www.alcoholandhealth.org1 journal club alcohol and health: current evidence september–october 2006

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Journal Club

Alcohol and Health: Current EvidenceSeptember–October 2006

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Featured Article

Comparison of the combined marker GGT-CDT and the conventional laboratory markers of alcohol

abuse in heavy drinkers, moderate drinkers and abstainers

Hietala J, et al. Alcohol Alcohol. Advance Access published on June 23, 2006; doi:10.1093/alcalc/agl050.

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Study Objective

• To assess whether combining gamma-glutamyltransferase (GGT) and carbohydrate-deficient transferrin (CDT) (GGT-CDT) is…

• better than using single biomarkers to detect heavy drinking

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Study Design

• Markers compared in the following 3 groups:

– 165 heavy drinkers* with alcohol dependence– 51 moderate drinkers– 35 abstainers

• 51 heavy drinkers had evidence of liver disease but not hepatitis B or C.

• 44 heavy drinkers were later assessed during supervised abstinence.

*Drank approximately 3–40 drinks per day

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Assessing Validity of an Article About Diagnostic

Tests

• Are the results valid?

• What are the results?

• Will the results help me in caring for my patients?

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Are the Results Valid?

• Was there an independent, blind comparison with a reference standard?

• Did the patient sample include an appropriate spectrum of patients to whom the diagnostic test will be applied in clinical practice?

• Did the results of the test being evaluated influence the decision to perform the reference standard?

• Were the methods for performing the test described in sufficient detail to permit replication?

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Was there an independent, blind comparison with a reference

standard?• Reference standard for heavy drinking:

– Alcohol consumption in heavy drinkers was determined by detailed interview using a Timeline Follow-back technique (a validated method).

– Consumption in moderate drinkers was determined by an unspecified questionnaire.

• Blinding:

– Blinding is not specified.

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Did the patient sample include an appropriate spectrum of patients to

whom the diagnostic test will be applied in clinical practice?

• The sample included heavy drinkers with alcohol dependence with and without liver disease, moderate drinkers, and abstainers.

• However…

– none of the subjects had hepatitis B or C, – the entire sample included only 38 women, – all heavy drinkers drank heavily frequently, and– most importantly, no heavy drinkers without

dependence were included.

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Did the results of the test being evaluated influence the decision

to perform the reference standard?

• The sequence of events is not specified.

• Both the evaluated test and reference standard were administered to all subjects included in this report.

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Were the methods for performing the test described in sufficient detail to permit

replication?

• Yes.

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What Are the Results?

• Are the likelihood ratios for the test results presented or data necessary for their calculation included?

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Are the likelihood ratios for the test results presented or data necessary for their calculation

included?• Yes:

– The sensitivity of GGT-CDT for detecting heavy drinking was 90% (specificity 98%) and exceeded that of the other biomarkers:

• 63% for CDT alone • 58% for GGT alone • 50% for alanine aminotransferase • 47% for aspartate aminotransferase • 45% for mean corpuscular volume

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Likelihood ratios for the test results (cont.)

• A positive GGT-CDT test had a likelihood ratio (LR) of 45 for heavy drinking.

• A negative GGT-CDT test had an LR of 0.1 for heavy drinking.

• The superior performance of GGT-CDT was not affected by the presence of liver disease.

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Will the Results Help Me in Caring for my Patients?

• Will the reproducibility of the test result and its interpretation be satisfactory in my setting?

• Are the results applicable to my patients?

• Will the results change my management strategy?

• Will patients be better off as a result of the test?

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Will the reproducibility of the test result and its interpretation

be satisfactory in my clinical setting?

• The GGT and CDT can be performed as described in the paper, and a formula for their combination is specified.

• The precision and accuracy of the test in this study

were provided and could be assessed locally.

• Thus, the reproducibility and interpretation could be satisfactory in settings that follow the same procedures.

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Are the results applicable to the patients in my practice?

• No detail regarding the practice setting is provided.

• Therefore, applicability is questionable or, at least, difficult to determine.

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Will the results change my management strategy?

• This study does not address how these tests should be integrated into practice.

– E.g., when should they be used in addition to or in lieu of questionnaires?

• As such, this study alone is unlikely to

change management strategies, though it does suggest the combined biomarker is more accurate than single blood tests.

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Will patients be better off as a result of the test?

• Since the study does not have management implications,…

– it is not clear whether patients will be better off.

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Summary/Clinical Resolution

• Combining biomarkers may be more fruitful than individual serum tests for detecting heavy drinking.

• This study has a number of limitations:

– Recruitment/subject sampling and selection details are not provided, making generalizability difficult to determine.

– The spectrum of subjects was limited, threatening validity.

– Blinding was not specified, and therefore not likely done.

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Summary/Clinical Resolution (cont.)

• Limitations (cont.):

– It is unknown whether some subjects who did not get the reference standard were excluded.

• Many questions remain about using combined biomarkers in clinical settings, such as…

– when they should be used instead of or in addition to questionnaires.