1. www.alcoholandhealth.org1 Journal Club Alcohol and Health: Current Evidence September–October 2006

2. www.alcoholandhealth.org2 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.

3. www.alcoholandhealth.org3 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

4. www.alcoholandhealth.org4 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

5. www.alcoholandhealth.org5 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?

6. www.alcoholandhealth.org6 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?

7. www.alcoholandhealth.org7 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.

8. www.alcoholandhealth.org8 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.

9. www.alcoholandhealth.org9 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.

10. www.alcoholandhealth.org10 Were the methods for performing the test described in sufficient detail to permit replication? Yes.

11. www.alcoholandhealth.org11 What Are the Results? Are the likelihood ratios for the test results presented or data necessary for their calculation included?

12. www.alcoholandhealth.org12 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

13. www.alcoholandhealth.org13 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.

14. www.alcoholandhealth.org14 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?

15. www.alcoholandhealth.org15 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.

16. www.alcoholandhealth.org16 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.

17. www.alcoholandhealth.org17 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.

18. www.alcoholandhealth.org18 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.

19. www.alcoholandhealth.org19 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.

20. www.alcoholandhealth.org20 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.