Supplementing claims data with outpatient laboratory test results to improve confounding adjustment in effectiveness studies of lipid-lowering treatments

  • Sebastian Schneeweiss1Email author,

    Affiliated with

    • Jeremy A Rassen1,

      Affiliated with

      • Robert J Glynn1,

        Affiliated with

        • Jessica Myers1,

          Affiliated with

          • Gregory W Daniel2,

            Affiliated with

            • Joseph Singer3,

              Affiliated with

              • Daniel H Solomon1,

                Affiliated with

                • SeoYoung Kim1,

                  Affiliated with

                  • Kenneth J Rothman1, 4,

                    Affiliated with

                    • Jun Liu1 and

                      Affiliated with

                      • Jerry Avorn1

                        Affiliated with

                        BMC Medical Research Methodology201212:180

                        DOI: 10.1186/1471-2288-12-180

                        Received: 22 May 2012

                        Accepted: 9 October 2012

                        Published: 26 November 2012

                        Abstract

                        Background

                        Adjusting for laboratory test results may result in better confounding control when added to administrative claims data in the study of treatment effects. However, missing values can arise through several mechanisms.

                        Methods

                        We studied the relationship between availability of outpatient lab test results, lab values, and patient and system characteristics in a large healthcare database using LDL, HDL, and HbA1c in a cohort of initiators of statins or Vytorin (ezetimibe & simvastatin) as examples.

                        Results

                        Among 703,484 patients 68% had at least one lab test performed in the 6 months before treatment. Performing an LDL test was negatively associated with several patient characteristics, including recent hospitalization (OR = 0.32, 95% CI: 0.29-0.34), MI (OR = 0.77, 95% CI: 0.69-0.85), or carotid revascularization (OR = 0.37, 95% CI: 0.25-0.53). Patient demographics, diagnoses, and procedures predicted well who would have a lab test performed (AUC = 0.89 to 0.93). Among those with test results available claims data explained only 14% of variation.

                        Conclusions

                        In a claims database linked with outpatient lab test results, we found that lab tests are performed selectively corresponding to current treatment guidelines. Poor ability to predict lab values and the high proportion of missingness reduces the added value of lab tests for effectiveness research in this setting.

                        Keywords

                        Insurance claims data Laboratory test results Serum lipid levels Confounding Imputation Pharmacoepidemiology Lipid lowering therapy Statin Ezetimibe

                        Background

                        Administrative health insurance claims databases provide comprehensive and longitudinal records of encounters with the health care system and of drug dispensing, but lack clinical detail. For example, while the performance of a lab test will generate a claim, the test result will not be available within the claims database. This shortcoming can be overcome by merging outpatient laboratory test results extracted from electronic medical records (EMR) systems with claims data. Adjusting for lab results may result in better confounding control when administrative claims data are used to study treatment effects of medical products.

                        A difficulty arises from the way in which lab tests are ordered and performed in the American health care system. EMR systems with outpatient lab results generally rely on major laboratory companies to supply lab results data; results for patients whose tests are conducted outside the large chains may go unrecorded in EMRs. In conducting comparative effectiveness research in claims data, pharmacoepidemiologists generally interpret the absence of a claim as the absence of that service/diagnosis, which can result in a covariate misclassification problem but not a missing data problem [1]. However, missing lab test results do not mean the test was not performed or the results are normal, and thus must be handled like other missing data. There is little guidance in the literature on the nature of the missingness of such laboratory information or whether missing lab test results can be adequately imputed.

                        Investigators have employed varying strategies to deal with this situation. One approach is to identify a subcohort of patients with complete information on the lab test results of interest. Seeger et al. studied the effectiveness of statin therapy to reduce myocardial infarction rates, by requiring all patients studied to have a recorded LDL > 130 mg/dl [2]. This approach reduces the proportion of subjects with missing data, but that advantage comes at the cost of fewer subjects in the study, and a final study population that may be dissimilar to the broader patient population for important characteristics. Furthermore, this approach is impractical for multiple unrelated lab test results, as complete cases may be few [3].

                        One unfavorable approach is to include an indicator term for missing lab test data. In the case of lab results, missingness can imply three things: (1) the physician did not see a need to have a test ordered; (2) the patient did not choose to have the test performed, or (3) the test was performed but not in a facility whose data fed back to the patient’s EMR (Figure 1). Though the implication of each of these cases is entirely different, they are indistinguishable in the data; as such, coding them simply as “missing” would lead to bias. Even if all the missingness were due to the third case, in which data are most plausibly missing completely at random, the use of a missing indicator term could still cause bias [4, 5].
                        http://static-content.springer.com/image/art%3A10.1186%2F1471-2288-12-180/MediaObjects/12874_2012_833_Fig1_HTML.jpg
                        Figure 1

                        Reasons for missing lab test results in a longitudinal healthcare utilization database linked to a lab test provider database*. * In the setting of a new user cohort study with a defined covariate assessment period before the first exposure and before follow-up

                        In order to further meaningful comparative effectiveness research, we must understand the selectiveness of missing lab test results and how missingness may be related to study outcomes. In this paper, we seek to describe the analytic issues encountered when lab results may not be available for many patients. As an example, we describe the characteristics associated with the absence of laboratory test results and the degree to which missingness and actual lab test values can be predicted based on patient and health plan characteristics in a population of patients initiating lipid-lowering therapy.

                        Methods

                        Database studies that combine claims and lab test results or other data from EMRs typically employ the claims as a “data backbone,” as claims data provide a longitudinal view of virtually all health care encounters and drug dispensings submitted for health insurance reimbursement. Increasingly, claims databases link data from large national lab test chains [68]. Though the chains service a large number of American patients, the resulting linked data may cover substantially less than 50% of outpatient lab tests, with coverage highly dependent on the region where the patient resides and the lab companies servicing that region. Figure 1 illustrates two levels of missingness that may arise in such situations. No claim will be recorded (Level 1) if a physician does not order a test, a patient receives a lab in a hospital, or a patient does not get a test that was ordered. The result of a test that was performed may not be transmitted to the patient’s claims data (Level 2) if the insurer has not established a data exchange agreement with the laboratory provider. The likelihood of Level 2 missingness increases if there is no laboratory provider operating in the area that has a data exchange agreement with the insurer.

                        Data sources

                        We employed longitudinal claims data from 14 Blue Cross and/or Blue Shield-licensed health plans of Wellpoint across 14 US states, as represented in the HealthCore Integrated Research DatabaseSM (HIRDSM). HealthCore linked claims information to lab test results provided by two large national laboratory providers, for laboratory tests performed between January 1, 2005 through June 30, 2010 on patients represented in the HIRD system. The claims data contained information on drug dispensings, outpatient medical services, and hospitalizations including emergency room visits. All medical services were coded with up to 9 discharge diagnoses [1]. Individual laboratory test results were identified by LOINC codes and standardized across lab providers. This study was approved by the Brigham and Women’s Hospital Institutional Review Board and signed data use agreements were in place.

                        Study cohort and exposure

                        From the data available, we established a cohort of all incident users of any statin (simvastatin, pravastatin, lovastatin, atorvastatin, rosuvastatin), Vytorin (simvastatin plus ezetimibe), or ezetimibe who were 18 years or older at the start of treatment. Incident use was established by requiring at least 12 months of insurance coverage before treatment and no use of any lipid-lowering therapy in those 12 months. 1 All covariate information was assessed in the longitudinal healthcare claims over a covariate assessment period (CAP) starting 6 months before treatment initiation and up to the day of dispensing of the index drug. Follow-up for occurrence of MI started 1 month after initiation of lipid-lowering treatment, a conservative assumption to allow for the biologic action of the medication to occur (Figure 2) [9]. We categorized each medication on the index date into high and low intensity treatment based on its ability to lower LDL levels (Table 1) [10].
                        http://static-content.springer.com/image/art%3A10.1186%2F1471-2288-12-180/MediaObjects/12874_2012_833_Fig2_HTML.jpg
                        Figure 2

                        Incident user cohort study*. * The 6-month covariate assessment period (CAP) precedes the initiation of treatment. During the CAP we identified patient characteristics, including lab tests performed and lab test results available. After treatment start followed a 1-month lag period before events were attributed to the treatment. The arrows between prescriptions (Rx), diagnoses (Dx) and lab tests denote the fact that the temporality of events within the CAP was not considered in this study

                        Table 1

                        Definitions for high vs. low intensity lipid-lowering therapy

                        Generic entity of study medications

                        Brand name

                        High-intensity daily doses (mg)

                        Low-intensity daily doses (mg)

                        Atorvastatin

                        Lipitor

                        > 10

                        ≤ 10

                        Fluvastatin

                        Lescol

                        All doses considered low-intensity

                        Lovastatin

                        Mevacor

                        > 40

                        ≤ 40

                        Pravastatin

                        Pravachol

                        All doses considered low-intensity

                        Rosuvastatin

                        Crestor

                        > 5

                        ≤ 5

                        Simvastatin

                        Zocor

                        > 40

                        ≤ 40

                        Ezetimibe

                        Zetia

                          

                        Ezetimibe + simvastatin fixed combination

                        Vytorin

                        If simvastatin component > 40

                        If simvastatin component ≤ 40

                        We defined two subgroups of patients with chronic conditions. Rheumatoid arthritis (RA) was defined as at least two outpatient diagnoses of RA in the CAP or one hospital discharge diagnosis of RA in CAP or one diagnosis of RA plus dispensing of a disease modifying anti-rheumatic drug. Diabetes (DM) was defined as at least two outpatient diagnoses of DM in the CAP or one hospital discharge diagnosis of DM in CAP or one diagnosis of DM plus an insulin or oral antidiabetic dispensing. Patients with rheumatoid arthritis and diabetes were identified as subgroups with chronic conditions because these patients were likely to receive more lab tests at regular intervals than the typical patient initiating a statin. Patients with rheumatoid arthritis are of further interest in that they may receive care primarily from a specialist rather than an internist and therefore, may have different patterns of laboratory use.

                        Patient characteristics and lab test results

                        Patient characteristics and potential confounders assessed during the 6-month CAP included age (18–40; 41–64; 65+), sex, state of residence, insurance plan type (Health Maintenance Organization, Medicare Advantage, Medicare Supplemental, Preferred Provider Organizations, Indemnity, other), number of physician visits, number of cardiologist visits, number of different drugs used, [11] hospitalization in the 30 days prior to treatment initiation, hospitalization for more than 30 days before treatment initiation, number of days hospitalized, number of outpatient lab test ordered, hypercholesterolemia, hypertension, heart failure, myocardial infarction, coronary revascularization, peripheral vascular disease, peripheral arterial revascularization, TIA/stroke, carotid revascularization, pre-diabetes, diabetes, arthritis, COPD, oxygen canister use, and obesity. Clinical covariates were assessed based on the presence of ICD-9 diagnosis codes (see Additional file 1: Appendix Table S1) in administrative claims during the CAP. In this exploratory analysis, we included a wide range of clinical covariates frequently measured in claims-based studies.

                        Within the 6 months covariate assessment period we identified all recorded outpatient lab test results for 23 commonly-performed lab tests, including lipid tests, HbA1c, and others (see Additional file 1: Appendix Table S2). Additionally, we used CPT-4 codes to identify all labs for which charges were claimed during the CAP. We chose to include 23 lab tests to increase the probability that patients would have multiple lab tests performed and that we would be able to asses whether lab values were missing at the patient level or the test level.

                        In comparative effectiveness research, as in other areas of clinical epidemiology, missing data are both common and problematic. Imputation of missing values may increase precision and validity of effect estimates. The imputation literature recommends including not only pre-exposure patient characteristics and treatment information in the prediction of missing values but also information on the outcome status [12]. In our example, outcomes of interest were the incidence of myocardial infarction (assessed with a positive predictive value of 94%); [13] hospitalization for acute coronary syndrome (ACS) that included a coronary revascularization procedure; stroke; and death attributed to any cause (see Additional file 1: Appendix Table S3). Follow-up time started 1 month after initiation of a cholesterol-lowering drug (Figure 2). Patients were censored at the time of discontinuation of the index drug, any of the outcomes, disenrollment, or study end (June 30, 2010), whichever came first.

                        Analysis

                        In this analysis, ascertainment of performing a lab test refers only to tests performed in the outpatient setting. We determined the proportion of patients who had at least one such lab test performed out of the 23 study lab tests and then focused on 3 specific cardiovascular risk markers: LDL, HDL, and HbA1c[14]. In sensitivity analyses, we extended the 6-month covariate assessment period to 9 and to 12 months in an effort to capture more lab test results.

                        In order to quantify differential lab test performance and result availability, we computed the number of lab tests performed (as measured by the presence of CPT-4 codes) and the proportion of those with test results available in the linked database. We then cross-tabulated these data with patient and system characteristics.

                        For each of the LDL, HDL, and HbA1c cardiovascular disease risk markers, any factors associated with a completed test were identified in a multivariate logistic regression that predicted whether the outpatient lab test was performed, as a function of the patient and system characteristics described above plus statin/Vytorin exposure and cardiovascular outcome status. We then determined overall sensitivity and specificity for the predicted probabilities of test performance and model c-statistics.

                        In order to explore the performance of imputation strategies, we fit linear regression models for the patients who had lab test results available, in order to predict the actual LDL, HDL, and HbA1c. In instances where patients received multiple tests, we used the value from the last test. We assumed normal distributions of test results as reasonable approximations, although data were slightly skewed. We express the proportion of explained variation as the observed R2 from the linear regression models.

                        Lastly, we investigated the relationship between the completion of a lab test, the availability of test results in our database, and whether the test results themselves differed between study exposure groups stratified by RA and diabetes.

                        Results

                        Over the study period we identified 703,484 patients who met the study eligibility criteria and initiated lipid-lowering therapy with statins, ezetimibe, or a combination of both. Among those, 68% had a recorded charge for at least one of the 23 study lab tests in the 6 months before treatment (Table 2). This proportion increased to 72% if the covariate assessment period was extended to 9 months before treatment, and to 74% during a 12-month period. For patients with diabetes or RA the proportions were higher (80% during 6 months) but showed equally small increases if the covariate assessment period was extended (83% and 84%). For LDL and HbA1c tests, the proportion of patients with a recorded charge for at least one test during the 6 months before initiation of lipid-lowering therapy was about 60% and 17%, respectively. For patients with diagnosed diabetes, 68% had a charge for an HbA1c test (Table 2).
                        Table 2

                        Number of patients with at least one lab test performed and claimed among 703,484 initiators of statins and/or ezetimibe using 6, 9, and 12-month confounder assessment periods (CAPs)

                         

                        All patients

                        Number (%) of patients with at least 1 lab test performed*

                        Number (%) of patients with at least 1 LDL lab test performed

                        Number (%) of patients with at least 1 LDL lab test performed

                        6 month CAP

                        9 month CAP

                        12 month CAP

                        6 month CAP

                        9 month CAP

                        12 month CAP

                        6 month CAP

                        9 month CAP

                        12 month CAP

                        N

                        %

                        N

                        %

                        N

                        %

                        N

                        %

                        N

                        %

                        N

                        %

                        N

                        %

                        N

                        %

                        N

                        %

                        All patients

                        703,484

                        481,133

                        68%

                        505,161

                        72%

                        520,559

                        74%

                        421,708

                        60%

                        445,205

                        63%

                        460,293

                        65%

                        121,764

                        17%

                        132,358

                        19%

                        139,784

                        20%

                        DM patients

                        111,684

                        89,344

                        80%

                        92,185

                        83%

                        93,952

                        84%

                        74,576

                        67%

                        78,598

                        70%

                        81,104

                        73%

                        76,413

                        68%

                        79,932

                        72%

                        81,965

                        73%

                        RA patients

                        4,523

                        3,676

                        81%

                        3,774

                        83%

                        3,840

                        85%

                        2,650

                        59%

                        2,813

                        62%

                        2,915

                        64%

                        839

                        19%

                        918

                        20%

                        984

                        22%

                        * All tests = any of a set of 23 different frequently-performed laboratory tests recorded in study database.

                        Overall and regardless of having a test performed, the proportion of patients with any outpatient lab test results available in the linked database was about 30%, which was similar in patients with diabetes or RA. Lab test results for LDL or HDL were available for about 20% of patients during the 6 months before initiation of lipid-lowering therapy.

                        Table 3 shows whether any of 23 outpatient lab tests, including LDL, HDL and HbA1c were performed within the 6 months before initiating lipid-lowering therapy cross-tabulated by a range of patient and health system characteristics. Overall, 481,133 (68%) of study patients had claims evidence of an outpatient lab test and 42% thereof had results available in the study data (29% of all patients). The proportion with at least one lab test performed varied substantially by patient characteristics, while test result availability varied little, and only for variables such as system characteristics and state of residence (Table 3).
                        Table 3

                        Patients with lab test results reported in study population of 703,484 initiators of statins or ezetimibe using a 6-month covariate assessment period*

                        Patient characteristics as determined in CAP

                        All patients

                        Patients with at least 1 of any 23 lab tests1)

                        Patients with at least 1 LDL test

                        Patients with at least 1 HDL test

                        Patients with at least 1 HbA1ctest

                         

                        Tests performed

                        Results available

                        Tests performed

                        Results available

                        Tests performed

                        Results available

                        Tests performed

                        Results available

                        N

                        N

                        % of total

                        N

                        % of total

                        % of done

                        N

                        %

                        N

                        %

                        % of performed

                        N

                        %

                        N

                        %

                        % of performed

                        N

                        %

                        N

                        %

                        % of performed

                        All patients

                        703,484

                        481,133

                        68

                        204,143

                        29

                        42

                        421,708

                        60

                        178,254

                        25

                        42

                        417,598

                        59

                        176,780

                        25

                        42

                        121,764

                        17

                        56,653

                        8

                        47

                        Age

                                             

                        18-40

                        71,396

                        52,674

                        74

                        23,861

                        33

                        45

                        48,565

                        68

                        21,313

                        30

                        44

                        48,021

                        67

                        21,150

                        30

                        44

                        12,424

                        17

                        5,770

                        8

                        46

                        41-64

                        489,581

                        363,406

                        74

                        150,096

                        31

                        41

                        329,097

                        67

                        131,999

                        27

                        40

                        325,945

                        67

                        130,912

                        27

                        40

                        92,076

                        19

                        40,635

                        8

                        44

                        65+

                        142,507

                        65,053

                        46

                        30,186

                        21

                        46

                        44,046

                        31

                        24,942

                        18

                        57

                        43,632

                        31

                        24,718

                        17

                        57

                        17,264

                        12

                        10,248

                        7

                        59

                        Male sex

                        378,177

                        256,537

                        68

                        107,876

                        29

                        42

                        225,308

                        60

                        94,715

                        25

                        42

                        223,007

                        59

                        93,962

                        25

                        42

                        66,202

                        18

                        30,286

                        8

                        46

                        # of days hospitalized

                        1

                        1

                         

                        1

                          

                        0

                        54

                        0

                        51

                        93

                        0

                        55

                        0

                        51

                        91

                        1

                        91

                        1

                        78

                        86

                        Hospitalized in 30 days before treatment initiation (y/n)

                        52,959

                        29,933

                        57

                        8,871

                        17

                        30

                        15,942

                        30

                        5,738

                        11

                        36

                        15,929

                        30

                        5,691

                        11

                        36

                        6,353

                        12

                        2,483

                        5

                        39

                        Hospitalized in 31 to 180 days before treatment initiation (y/n)

                        39,304

                        28,823

                        73

                        10,569

                        27

                        37

                        18,889

                        48

                        7,546

                        19

                        40

                        18,790

                        48

                        7,491

                        19

                        40

                        7,852

                        20

                        3,405

                        9

                        43

                        Any coronary hospitalization**

                        43,507

                        25,909

                        60

                        7,468

                        17

                        29

                        13,821

                        32

                        4,911

                        11

                        36

                        13,775

                        32

                        4,869

                        11

                        35

                        5,545

                        13

                        2,100

                        5

                        38

                        # of cardiologist visits

                        0

                        0

                         

                        0

                          

                        0

                         

                        0

                          

                        0

                         

                        0

                          

                        0

                         

                        0

                          

                        # of other physician visits

                        3

                        4

                         

                        3

                          

                        3

                         

                        3

                          

                        3

                         

                        3

                          

                        4

                         

                        3

                          

                        Number of different drugs

                        4

                        4

                         

                        4

                          

                        4

                         

                        4

                          

                        4

                         

                        4

                          

                        6

                         

                        5

                          

                        # of lab tests performed

                        6

                        9

                         

                        7

                          

                        9

                         

                        6

                          

                        9

                         

                        6

                          

                        12

                         

                        8

                          

                        Vascular conditions:

                                             

                        Hypercholesterolemia

                        358,649

                        308,261

                        86

                        100,890

                        28

                        33

                        286,144

                        80

                        88,027

                        25

                        31

                        282,875

                        79

                        87,016

                        24

                        31

                        74,655

                        21

                        23,200

                        6

                        31

                        Hypertension

                        351,542

                        244,573

                        70

                        100,813

                        29

                        41

                        207,406

                        59

                        85,722

                        24

                        41

                        205,531

                        58

                        84,903

                        24

                        41

                        75,677

                        22

                        33,388

                        9

                        44

                        Heart failure

                        16,008

                        10,057

                        63

                        3,243

                        20

                        32

                        5,082

                        32

                        1,917

                        12

                        38

                        5,064

                        32

                        1,891

                        12

                        37

                        2,884

                        18

                        1,089

                        7

                        38

                        Acute MI

                        20,797

                        11,127

                        54

                        2,673

                        13

                        24

                        5,074

                        24

                        1,709

                        8

                        34

                        5,046

                        24

                        1,698

                        8

                        34

                        1,966

                        9

                        714

                        3

                        36

                        Old MI

                        5,166

                        3,734

                        72

                        998

                        19

                        27

                        2,345

                        45

                        714

                        14

                        30

                        2,320

                        45

                        705

                        14

                        30

                        873

                        17

                        293

                        6

                        34

                        Acute coron. syndrome

                        63,781

                        40,721

                        64

                        12,776

                        20

                        31

                        25,407

                        40

                        9,242

                        14

                        36

                        25,206

                        40

                        9,155

                        14

                        36

                        9,328

                        15

                        3,791

                        6

                        41

                        TIA/stroke

                        16,747

                        9,764

                        58

                        3,086

                        18

                        32

                        5,731

                        34

                        2,098

                        13

                        37

                        5,692

                        34

                        2,080

                        12

                        37

                        2,255

                        13

                        845

                        5

                        37

                        Carotid revasc3)

                        888

                        598

                        67

                        193

                        22

                        32

                        370

                        42

                        134

                        15

                        36

                        369

                        42

                        135

                        15

                        37

                        137

                        15

                        50

                        6

                        36

                        PVD

                        8,032

                        5,489

                        68

                        1,868

                        23

                        34

                        3,241

                        40

                        1,300

                        16

                        40

                        3,260

                        41

                        1,284

                        16

                        39

                        1,515

                        19

                        642

                        8

                        42

                        Coronary revasc2)

                        22,575

                        13,317

                        59

                        3,581

                        16

                        27

                        7,098

                        31

                        2,377

                        11

                        33

                        7,069

                        31

                        2,351

                        10

                        33

                        2,610

                        12

                        942

                        4

                        36

                        Peripheral revas

                        987

                        748

                        76

                        261

                        26

                        35

                        388

                        39

                        171

                        17

                        44

                        394

                        40

                        170

                        17

                        43

                        204

                        21

                        90

                        9

                        44

                        Diabetes

                        111,684

                        89,344

                        80

                        34,137

                        31

                        38

                        74,576

                        67

                        28,032

                        25

                        38

                        73,937

                        66

                        27,693

                        25

                        37

                        76,413

                        68

                        26,959

                        24

                        35

                        Pre-diabetes

                        9,916

                        8,941

                        90

                        2,559

                        26

                        29

                        7,957

                        80

                        2,032

                        20

                        26

                        7,877

                        79

                        2,016

                        20

                        26

                        6,258

                        63

                        1,569

                        16

                        25

                        Rheumatoid arthritis

                        4,523

                        3,676

                        81

                        1,520

                        34

                        41

                        2,650

                        59

                        935

                        21

                        35

                        2,620

                        58

                        926

                        20

                        35

                        839

                        19

                        315

                        7

                        38

                        Recorded obesity

                        20,533

                        17,354

                        85

                        5,295

                        26

                        31

                        15,138

                        74

                        4,307

                        21

                        28

                        14,971

                        73

                        4,251

                        21

                        28

                        6,897

                        34

                        1,956

                        10

                        28

                        COPD

                        27,318

                        18,918

                        69

                        6,382

                        23

                        34

                        13,236

                        48

                        4,855

                        18

                        37

                        13,144

                        48

                        4,818

                        18

                        37

                        4,557

                        17

                        1,708

                        6

                        37

                        Use of oxygen tank

                        105

                        59

                        56

                        20

                        19

                        34

                        41

                        39

                        13

                        12

                        32

                        42

                        40

                        13

                        12

                        31

                        20

                        19

                        8

                        8

                        40

                        Plan type: Indemnity

                        3,942

                        3,391

                        86

                        807

                        20

                        24

                        3,149

                        80

                        696

                        18

                        22

                        3,132

                        79

                        698

                        18

                        22

                        823

                        21

                        181

                        5

                        22

                        HMO

                        202,910

                        109,821

                        54

                        100,426

                        49

                        91

                        95,306

                        47

                        92,427

                        46

                        97

                        94,360

                        47

                        91,683

                        45

                        97

                        28,471

                        14

                        30,241

                        15

                        106

                        Medicare Advantage

                        62,459

                        37,744

                        60

                        24,757

                        40

                        66

                        28,014

                        45

                        20,468

                        33

                        73

                        27,758

                        44

                        20,304

                        33

                        73

                        11,658

                        19

                        8,622

                        14

                        74

                        Medicare Supplemental

                        43,645

                        15,519

                        36

                        1,294

                        3

                        8

                        7,822

                        18

                        1,000

                        2

                        13

                        7,745

                        18

                        994

                        2

                        13

                        2,647

                        6

                        285

                        1

                        11

                        Other

                        22,274

                        10,323

                        46

                        4,057

                        18

                        39

                        8,677

                        39

                        3,486

                        16

                        40

                        8,593

                        39

                        3,456

                        16

                        40

                        2,422

                        11

                        1,153

                        5

                        48

                        Preferred Provider Org.

                        368,254

                        304,335

                        83

                        72,802

                        20

                        24

                        278,740

                        76

                        60,177

                        16

                        22

                        276,010

                        75

                        59,645

                        16

                        22

                        75,743

                        21

                        16,171

                        4

                        21

                        State of residence: 1

                        194,150

                        97,286

                        50

                        51,523

                        27

                        53

                        83,875

                        43

                        46,332

                        24

                        55

                        82,694

                        43

                        46,342

                        24

                        56

                        25,050

                        13

                        16,146

                        8

                        64

                        2

                        23,642

                        20,159

                        85

                        9,281

                        39

                        46

                        18,674

                        79

                        8,517

                        36

                        46

                        18,678

                        79

                        8,521

                        36

                        46

                        5,416

                        23

                        2,352

                        10

                        43

                        3†

                        5,006

                        3,783

                        76

                        359

                        7

                        9

                        3,420

                        68

                        318

                        6

                        9

                        3,395

                        68

                        311

                        6

                        9

                        923

                        18

                        85

                        2

                        9

                        4

                        64,242

                        53,997

                        84

                        30,197

                        47

                        56

                        49,458

                        77

                        27,231

                        42

                        55

                        48,892

                        76

                        26,855

                        42

                        55

                        13,198

                        21

                        7,569

                        12

                        57

                        5

                        36,365

                        29,200

                        80

                        4,805

                        13

                        16

                        25,522

                        70

                        3,635

                        10

                        14

                        25,903

                        71

                        3,604

                        10

                        14

                        6,872

                        19

                        917

                        3

                        13

                        6

                        48,045

                        37,348

                        78

                        8,630

                        18

                        23

                        32,056

                        67

                        6,583

                        14

                        21

                        31,752

                        66

                        6,476

                        13

                        20

                        8,929

                        19

                        1,723

                        4

                        19

                        7

                        13,847

                        11,833

                        85

                        359

                        3

                        3

                        10,773

                        78

                        260

                        2

                        2

                        10,647

                        77

                        259

                        2

                        2

                        2,678

                        19

                        44

                        0

                        2

                        8

                        28,450

                        23,108

                        81

                        6,178

                        22

                        27

                        20,781

                        73

                        5,309

                        19

                        26

                        20,627

                        73

                        5,276

                        19

                        26

                        5,877

                        21

                        1,461

                        5

                        25

                        9

                        8,703

                        7,401

                        85

                        1,089

                        13

                        15

                        6,789

                        78

                        875

                        10

                        13

                        6,772

                        78

                        886

                        10

                        13

                        1,812

                        21

                        243

                        3

                        13

                        10†

                        3,753

                        2,464

                        66

                        1,183

                        32

                        48

                        2,226

                        59

                        1,097

                        29

                        49

                        2,188

                        58

                        1,083

                        29

                        49

                        710

                        19

                        369

                        10

                        52

                        11

                        4,864

                        3,610

                        74

                        2,310

                        47

                        64

                        3,217

                        66

                        2,030

                        42

                        63

                        3,137

                        64

                        2,029

                        42

                        65

                        1,015

                        21

                        648

                        13

                        64

                        12

                        64,237

                        24,644

                        38

                        36,009

                        56

                        146

                        15,190

                        24

                        32,988

                        51

                        217

                        14,979

                        23

                        32,722

                        51

                        218

                        6,068

                        9

                        12,646

                        20

                        208

                        13

                        85,926

                        71,455

                        83

                        22,481

                        26

                        31

                        63,065

                        73

                        18,108

                        21

                        29

                        62,703

                        73

                        17,993

                        21

                        29

                        19,587

                        23

                        5,464

                        6

                        28

                        Other

                        44,110

                        35,064

                        79

                        5,628

                        13

                        16

                        31,850

                        72

                        4,867

                        11

                        15

                        31,462

                        71

                        4,839

                        11

                        15

                        8,949

                        20

                        1,446

                        3

                        16

                        14†

                        3,804

                        3,311

                        87

                        116

                        3

                        4

                        3,113

                        82

                        100

                        3

                        3

                        3,107

                        82

                        99

                        3

                        3

                        876

                        23

                        31

                        1

                        4

                        15

                        74,340

                        56,470

                        76

                        23,995

                        32

                        42

                        51,699

                        70

                        20,004

                        27

                        39

                        50,662

                        68

                        19,485

                        26

                        38

                        13,804

                        19

                        5,509

                        7

                        40

                        * Study period starts July 1, 2005, ensuring a minimum CAP of 6 months with lab test results coverage and a pre-CAP of 6 months.

                        ** Hospitalization with primary discharge code for acute MI, ACS, PCTA, PCI, CABG.

                        † States with no WellPoint presence.

                        1) This is limited to 23 lab test results reported in our study database.

                        2) PCTA, PCI, CABG.

                        3) Carotid stent, carotid endarterectomy.

                        Having been hospitalized in the 30 days before the initiation of lipid-lowering treatment was negatively associated with receiving an outpatient test, likely because the relevant lab tests were performed during the hospitalization and as such do not appear as outpatient lab tests. Some patients hospitalized for acute coronary syndrome or MI may have received lipid-lowering therapy for secondary prevention without the need for a lab test. This is supported by the fact that patients with both recent MI and ACS had a lower than average proportion with at least one test performed (24% and 40% compared with an average of 68%). A code for hypercholesterolemia is frequently accompanied by an LDL test performed (80%) likely because the test ordering is accompanied with such a billing code.

                        Patients with Medicare Supplemental coverage (43,645) had a much lower proportion of claims for LDL tests performed (18%), and of those only 2% had results available. The lab test provider may not have included the secondary payer on the claim.

                        The two lab test providers that provided data to the insurer do not operate in some states; for example, the availability of lab test results in one state was as low as 2% for LDL. Such low recording would not be dependent directly on patient characteristics as it affects an entire state and is driven by factors other than health status, though clinically relevant patient characteristics have varying prevalences across states.

                        Some patients resided in states not primarily covered by the health plan studied, and are covered only via accounts for nationally operating businesses (e.g., if the employer is based in another state, all employees may be members of a health plan in that other state, rather than the state of residence). For these patients, the availability of LDL test results is less than 10%. One state (#12) stands out as having a small proportion of patients with an outpatient LDL test performed (24%), but a much larger proportion of patients have a result available (51%). In this state, a larger proportion of providers are under HMO capitation agreements. Within these plans, under-recording of tests performed may be the result of bundled payment arrangements; however, results are still forwarded by the lab test providers resulting in the paradox of having more lab test results available in our database than performed as recorded in claims data. Among patients with Diabetes or RA, we found fundamentally similar results. Among elderly patients lab test results were more likely to be available among Medicare advantage enrollees than those patients covered through Medicare supplemental insurance (Table 4).
                        Table 4

                        Cross-tabulation between states and Medicare Advantage and Medicare Supplement status

                         

                        Patients with at least 1 of any 23 lab tests1)

                         

                        Patients in HMO or PPO

                        Patients in Medicare Advantage

                        Patients in Medicare Supplemental

                        State

                        Tests performed

                        Results available

                        Tests performed

                        Results available

                        Tests performed

                        Results available

                         

                        N

                        % of total

                        N

                        % of total

                        % of done

                        N

                        % of total

                        N

                        % of total

                        % of done

                        N

                        % of total

                        N

                        % of total

                        % of done

                        1

                        87,110

                        52

                        48,838

                        29

                        56

                        3,999

                        51

                        1,978

                        25

                        49

                        5,881

                        31

                        625

                        3

                        11

                        2

                        17,068

                        89

                        8,331

                        43

                        49

                        174

                        85

                        95

                        46

                        55

                        574

                        37

                        92

                        6

                        16

                        3†

                        3,507

                        81

                        329

                        8

                        9

                        16

                        44

                        12

                        33

                        75

                        141

                        39

                        3

                        1

                        2

                        4

                        53,350

                        86

                        30,037

                        48

                        56

                        112

                        84

                        64

                        48

                        57

                        519

                        26

                        92

                        5

                        18

                        5

                        26,240

                        84

                        4,454

                        14

                        17

                        1,036

                        80

                        167

                        13

                        16

                        999

                        38

                        55

                        2

                        6

                        6

                        30,291

                        86

                        7,265

                        21

                        24

                        2,850

                        79

                        1,139

                        32

                        40

                        4,012

                        45

                        185

                        2

                        5

                        7

                        11,050

                        89

                        346

                        3

                        3

                        0

                        0

                        1

                        100

                        0

                        564

                        47

                        6

                        1

                        1

                        8

                        22,277

                        85

                        6,068

                        23

                        27

                        4

                        14

                        7

                        24

                        175

                        692

                        34

                        71

                        3

                        10

                        9

                        6,449

                        89

                        1,003

                        14

                        16

                        0

                        0

                        0

                        0

                        0

                        278

                        40

                        8

                        1

                        3

                        10†

                        2,372

                        66

                        1,144

                        32

                        48

                        3

                        23

                        5

                        38

                        167

                        5

                        31

                        0

                        0

                        0

                        11

                        3,547

                        76

                        2,289

                        49

                        65

                        1

                        33

                        2

                        67

                        200

                        38

                        21

                        9

                        5

                        24

                        12

                        15,645

                        43

                        19,387

                        54

                        124

                        6,560

                        30

                        14,189

                        65

                        216

                        105

                        39

                        15

                        6

                        14

                        13

                        46,115

                        86

                        15,049

                        28

                        33

                        22,884

                        84

                        7,035

                        26

                        31

                        1,543

                        39

                        126

                        3

                        8

                        Other

                        32,651

                        81

                        5,515

                        14

                        17

                        54

                        39

                        54

                        39

                        100

                        153

                        37

                        5

                        1

                        3

                        14†

                        3,256

                        88

                        113

                        3

                        3

                        0

                        0

                        0

                        0

                        0

                        7

                        30

                        0

                        0

                        0

                        15

                        53,228

                        82

                        23,060

                        36

                        43

                        51

                        59

                        9

                        10

                        18

                        8

                        33

                        2

                        8

                        25

                        † States with no WellPoint presence.

                        Based on patient and system characteristics plus exposure and outcome status it was possible to predict with high sensitivity (97%) and specificity (94%) whether outpatient lab tests were performed in the 6 months before treatment initiation. The corresponding model c-statistics of the logistic regression models were between 0.89 and 0.93 (Figure 3), indicating a very high predictive capacity. Strong independent associates of having an outpatient LDL test performed were a diagnosis of hypercholesterolemia or obesity, and carotid revascularization. Associates of low probability of doing LDL lab tests were recent hospitalization and being diagnosed with RA. Being older than 65 also decreased the chance of an LDL lab test, likely because of test underreporting due to bundled payments. Initiating high-intensity lipid-lowering treatment and dying in the study follow-up period were correlates of not having an outpatient LDL, HDL, or HBA1c test performed. Not surprisingly, the strongest predictor of having an HBA1c test performed was a diagnosis of diabetes or pre-diabetes.
                        http://static-content.springer.com/image/art%3A10.1186%2F1471-2288-12-180/MediaObjects/12874_2012_833_Fig3_HTML.jpg
                        Figure 3

                        Associates of selected outpatient lab tests performed in patients initiating lipid-lowering treatment according to claims data in 703,484 patients from a logistic regression model (darker means stronger association)

                        Among the patients for whom LDL, HDL, or HBA1c test levels were available, we then attempted to predict the actual lab levels based on their recorded patient and system characteristics. Using all observed factors described above, 17% of the variation could be explained (Figure 4). Young age was the strongest correlate of increased high LDL (+20 mg/dl) and HbA1c (+0.5%) levels, suggesting that in younger age initiation of lipid-lowering therapy was more driven by lab test results, i.e. primary prevention, while in older age past coronary events and other risk factors were the triggers for statin initiation despite lower LDL levels (−17 mg/dl).
                        http://static-content.springer.com/image/art%3A10.1186%2F1471-2288-12-180/MediaObjects/12874_2012_833_Fig4_HTML.jpg
                        Figure 4

                        Correlates of selected lab test results among patients with lab test results available (darker means stronger correlations)

                        Higher intensity of lipid lowering treatment generally was correlated with a lower proportion of outpatient LDL tests performed, a lower fraction of LDL test results available in the database, and lower LDL serum levels (Table 5). For example, among high dose simvastatin initiators (>40 mg/day), 52% had an outpatient LDL test performed before treatment start (63% for lower dose simvastatin). Of those patients, 37% had a test result available (42%), and the mean LDL serum level was 135.6 mg/dl compared to 147.3 mg/dl for patients started on low-intensity simvastatin. Mean LDL levels were generally lower in patients with diabetes who initiated lipid-lowering therapy.
                        Table 5

                        LDL tests performed and LDL test results available by lipid lowering treatment in patients initiating lipid-lowering therapy, including patient subgroups with diabetes (DM) or rheumatoid arthritis (RA)

                          

                        All patients

                        LDL test performed

                        LDL test results available

                        LDL level

                        HDL level

                         

                        Initiated medication

                        N

                        %

                        N

                        %

                        N

                        % of total N

                        % of ordered

                        mean

                        s.d.

                        mean

                        s.d.

                        All

                        Any statin alone

                        655,211

                        93

                        395,496

                        60.4

                        165,380

                        25.2

                        41.8

                        145.3

                        38.6

                        50.2

                        14.5

                         

                        Any statin high intensity*

                        173,979

                        25

                        98,309

                        56.5

                        41,320

                        23.7

                        42.0

                        144.2

                        45.5

                        49.2

                        14.3

                         

                        Any statin low intensity

                        481,232

                        68

                        297,187

                        61.8

                        124,060

                        25.8

                        41.7

                        145.7

                        36

                        50.6

                        14.6

                         

                        Simvastatin alone

                        282,658

                        40

                        176,697

                        62.5

                        73,193

                        25.9

                        41.4

                        147.0

                        36.3

                        50.2

                        14.4

                         

                        Simvastatin high dose (>40 mg)

                        11,354

                        2

                        5,912

                        52.1

                        2,192

                        19.3

                        37.1

                        135.6

                        49.5

                        48

                        13.6

                         

                        Simvastatin low dose

                        271,304

                        39

                        170,785

                        62.9

                        71,001

                        26.2

                        41.6

                        147.3

                        35.8

                        50.2

                        14.4

                         

                        Vytorin alone

                        24,931

                        4

                        12,966

                        52

                        6,820

                        27.4

                        52.6

                        142.2

                        47.6

                        49.6

                        14.3

                         

                        Vytorin high dose (>40 mg simvast)

                        1,069

                        0

                        563

                        52.7

                        223

                        20.9

                        39.6

                        124.1

                        56.7

                        48.1

                        13.5

                         

                        Vytorin low dose

                        23,862

                        3

                        12,403

                        52

                        6,597

                        27.6

                        53.2

                        142.8

                        47.1

                        49.6

                        14.4

                         

                        Ezetimibe alone

                        20,509

                        3

                        11,412

                        55.6

                        5,334

                        26

                        46.7

                        143.2

                        38.1

                        51.5

                        14.9

                         

                        Ezetimibe + statin

                        2,833

                        0

                        1,834

                        64.7

                        720

                        25.4

                        39.3

                        145.7

                        47.7

                        48.2

                        13.5

                         

                        Total:

                        703,484

                                  

                        DM

                        Any statin alone

                        103,664

                        93

                        69,788

                        67.3

                        25,927

                        25

                        37.2

                        124.8

                        37.4

                        46.5

                        13.1

                         

                        Any statin high intensity*

                        28,472

                        26

                        18,069

                        63.5

                        6,909

                        24.3

                        38.2

                        122.3

                        43.3

                        45.8

                        13.1

                         

                        Any statin low intensity

                        75,192

                        67

                        51,719

                        68.8

                        19,018

                        25.3

                        36.8

                        125.7

                        35.0

                        46.8

                        13.1

                         

                        Simvastatin alone

                        46,414

                        42

                        32,207

                        69.4

                        11,670

                        25.1

                        36.2

                        126.8

                        35.6

                        46.5

                        13.0

                         

                        Simvastatin high dose (>40 mg)

                        2,498

                        2

                        1,513

                        60.6

                        521

                        20.9

                        34.4

                        117.1

                        46.2

                        45.6

                        12.6

                         

                        Simvastatin low dose

                        43,916

                        39

                        30,694

                        69.9

                        11,149

                        25.4

                        36.3

                        127.2

                        35.0

                        46.6

                        13.0

                         

                        Vytorin alone

                        4,049

                        4

                        2,324

                        57.4

                        1,086

                        26.8

                        46.7

                        122.9

                        44.4

                        45.6

                        13.4

                         

                        Vytorin high dose (>40 mg simvast)

                        269

                        0

                        169

                        62.8

                        58

                        21.6

                        34.3

                        105.6

                        41.6

                        46.3

                        14.0

                         

                        Vytorin low dose

                        3,780

                        3

                        2,155

                        57

                        1,028

                        27.2

                        47.7

                        123.8

                        44.4

                        45.6

                        13.4

                         

                        Ezetimibe alone

                        3,459

                        3

                        2,092

                        60.5

                        884

                        25.6

                        42.3

                        126.9

                        37.7

                        47.0

                        13.1

                         

                        Ezetimibe + statin

                        512

                        1

                        372

                        72.7

                        135

                        26.4

                        36.3

                        133.1

                        44.5

                        44.8

                        11.8

                         

                        Total:

                        111,684

                                  

                        RA

                        Any statin alone

                        4,118

                        91

                        2,425

                        58.9

                        833

                        20.2

                        34.4

                        138.5

                        39.4

                        54.7

                        16.5

                         

                        Any statin high intensity*

                        1,044

                        23

                        575

                        55.1

                        205

                        19.6

                        35.7

                        135.4

                        50.9

                        53.6

                        17.8

                         

                        Any statin low intensity

                        3,074

                        68

                        1,850

                        60.2

                        628

                        20.4

                        33.9

                        139.5

                        34.8

                        55.1

                        16.0

                         

                        Simvastatin alone

                        1,749

                        39

                        1,070

                        61.2

                        360

                        20.6

                        33.6

                        141.6

                        33.4

                        54.3

                        15.5

                         

                        Simvastatin high dose (>40 mg)

                        70

                        2

                        37

                        52.9

                        14

                        20

                        37.8

                        134.6

                        44.2

                        46.5

                        12.0

                         

                        Simvastatin low dose

                        1,679

                        37

                        1,033

                        61.5

                        346

                        20.6

                        33.5

                        141.9

                        32.9

                        54.6

                        15.6

                         

                        Vytorin alone

                        174

                        4

                        85

                        48.9

                        43

                        24.7

                        50.6

                        142.6

                        45.6

                        52.8

                        16.3

                         

                        Vytorin high dose (>40 mg simvast)

                        9

                        0

                        4

                        44.4

                        2

                        22.2

                        50.0

                        177.0

                        76.4

                        52

                        22.6

                         

                        Vytorin low dose

                        165

                        4

                        81

                        49.1

                        41

                        24.8

                        50.6

                        141.0

                        44.5

                        52.8

                        16.3

                         

                        Ezetimibe alone

                        210

                        5

                        126

                        60

                        55

                        26.2

                        43.7

                        137.5

                        31.3

                        56.8

                        16.7

                         

                        Ezetimibe + statin

                        21

                        1

                        14

                        66.7

                        4

                        19

                        28.6

                        144.0

                        45.5

                        49.0

                        10.4

                         

                        Total:

                        4,523

                                  

                        * See methods section for definition.

                        Discussion

                        We studied the characteristics of laboratory test information in a pharmacoepidemiologic research data source that enriches longitudinal claims data with outpatient lab test results data, which makes it possible to better adjust for biomarkers of cardiac risk in comparative effectiveness studies. In an example cohort study of 703,484 patients initiating various lipid-lowering therapies, 68% of patients had at least one of a set of 23 study lab tests performed in the 6 months before treatment, and 42% of those had test results available. LDL test results were available for 24% of statin initiators, a non-trivial level of missingness that needed to be addressed in order to preserve the validity and generalizability of findings. Missingness due to absence of lab tests being performed followed a complex pattern that is largely explained by hospitalization, clinical practice guidelines which differ for primary and secondary prevention of coronary heart disease, and by some health care system characteristics.

                        Several key points regarding these patterns arose and have implications for conducting comparative effectiveness research studies in such enriched data sources.

                        Operational aspects

                        A covariate assessment period of 6 months was sufficient to capture the majority of outpatient lab tests performed. Extending the period to 9 and 12 months, and thus extending the required pre-exposure enrollment period, provided few additional observed lab tests but may disproportionally reduce the cohort size if working with health plans that have high enrollee turnover rates. Patients with existing chronic conditions like RA or diabetes have more outpatient lab tests available if their healthcare providers monitor them more closely. Recent hospitalizations strongly decreased the number of outpatient lab tests. It is likely that tests were performed during the hospitalization, and if the test results were available to the patient's primary care physician, repeating testing may not have been required for some time after discharge.

                        Selectiveness of lab tests performed

                        Patients with risk factors for cardiovascular events were less likely to have lab tests performed. Many patients with these characteristics receive lipid-lowering treatment as secondary prevention, which is initiated independent of serum lipid-levels more frequently than is primary prevention. Indeed, treatment guidelines in place since the late 1990s recommend that patients with a major cardiac event should be treated with lipid lowering medications [15, 16]. In a prior study, patients who initiated high-intensity lipid-lowering treatment were less likely to have had an outpatient lab test performed [17]. Because the presence of preexisting cardiac risk factors is both a strong predictor of future events and a predictor of missing data on lipid levels, disregarding the missing information can be expected to bias findings of non-randomized comparative effectiveness research in this setting.

                        Selectiveness of lipid lab test results available

                        Among patients who had lab test result available, those who were subsequently initiated on higher-intensity lipid-lowering treatment were more likely to have lower lipid serum levels. This finding is again compatible with clinical practice and trial findings that patients with acute coronary events (who are less likely to have outpatient lipid tests available) should be treated with high-intensity statins largely independent of their lipid levels [17, 18]. System factors like state of residence and insurance plan type, particularly supplemental insurance, may substantially influence the availability of test results. However, since those factors are less likely to be systematically related to health outcomes it is unlikely that these will act as major confounding factors in comparative effectiveness studies.

                        In addition to these limitations regarding lab tests, baseline clinical conditions may be under-reported through claims data in some patients, particularly when using a short ascertainment period, such as the 6-month period we used. For LDL, HDL, and HBA1c tests it is unlikely that point-of-care testing would be performed, which the lab test provider chain would not record. However, other tests, like INR, urine analyses and creatinine levels might be subject to this additional limitation.

                        If replicated in other patient populations and datasets, these findings have important implications for CER studies. The complexity of the nature of missingness that logically follows from clinical practice and the reality of our health care system requires the inclusion of a wide variety of patient and system characteristics in order to model the missing data structure. In our specific example the combination of primary and secondary prevention with lipid-lowering medications seems to complicate the prediction of missing values, but in the end is likely a reason why we could differentiate so well between patients who have an outpatient LDL test performed versus not (Figure 5). Once the outpatient lab test results were available, we had moderate ability to predict the exact lipid/HbA1c serum level. The resulting mismeasurement of imputed lab test results suggests that imputation of test results would provide only limited additional confounding control. However, estimation precision would be increased because the analyzable population would more than triple in our example study.
                        http://static-content.springer.com/image/art%3A10.1186%2F1471-2288-12-180/MediaObjects/12874_2012_833_Fig5_HTML.jpg
                        Figure 5

                        Ability of longitudinal claims data to predict whether a lab test was performed, a test result was available, and the actual serum level for three biomarkers of cardiovascular risk*. * c-statistics were computed from multivariate logistic regression models including patient factors measured during 6 months before lipid-lowering treatment initiation; r2 measured were computed only among patients who had a lab test result available from linear regression including patient factors measured during 6 months before lipid-lowering treatment initiation, actual treatment choice, as well as cardiovascular events and death during follow-up

                        It is likely that the specific patterns of missingness of outpatient lab test results will vary depending on the clinical scenario, health care practice, and system constraints. It is encouraging that despite the non-random missingness we were able to predict quite well who would and would not receive a lab test result, which is a good starting point for addressing this issue. However, our difficulty in predicting actual lab values is a challenge to incorporating lab data through imputation or weighting approaches in comparative effectiveness research studies.

                        Conclusion

                        In a claims database linked with outpatient lab test results, we found that lab tests are performed selectively depending on patient risk factors and corresponding to current treatment guidelines. Poor ability to predict lab values and the high proportion of missingness reduces the added value of lab tests for effectiveness research in this setting.

                        Disclosures

                        Dr. Schneeweiss is Principal Investigator of the Brigham and Women’s Hospital DEcIDE Center on Comparative Effectiveness Research and the DEcIDE Methods Center both funded by AHRQ and of the Harvard-Brigham Drug Safety and Risk Management Research Center funded by FDA. Dr. Schneeweiss is paid consultant to WHISCON and Booz & Co, and he is principal investigator of investigator initiated grants to the Brigham and Women’s Hospital from Pfizer, Novartis, and Boehringer-Ingelheim. Drs. Daniel was and Singer is employed by HealthCore, a subsidiary of WellPoint.

                        Declarations

                        Acknowledgements

                        Funded by HealthCore Inc. through the Brigham-HealthCore Methods Development Collaboration, the National Library of Medicine (RO1-LM010213), the National Center for Research Resources (RC1-RR028231) and the National Heart Lung and Blood Institute (RC4-HL106373). Dr. Rassen was supported by a career development award from AHRQ (K01-HS018088).

                        Many people have contributed to the understanding of the data sources and helped interpret the data: Marcus Wilson, PharmD, Peter Wahl, MA, MSCE, Niteesh K. Choudhry MD, PhD.

                        Authors’ Affiliations

                        (1)
                        Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital
                        (2)
                        The Brookings Institution
                        (3)
                        HealthCore Inc
                        (4)
                        RTI Health Solutions, RTP

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                        19. Pre-publication history

                          1. The pre-publication history for this paper can be accessed here:http://​www.​biomedcentral.​com/​1471-2288/​12/​180/​prepub

                        Copyright

                        © Schneeweiss et al.; licensee BioMed Central Ltd. 2012

                        This article is published under license to 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.