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An evaluation of central laboratories in three VA cooperative studies
P Peduzzi1, P Hartigan, G Johnson
1Cooperative Studies Program Coordinating Center, VA Medical Center, West Haven, CT 06516.
Insights
Central labs are not always cost-effective for clinical measurements in trials. While prudent in two studies, central electrocardiogram analysis for myocardial infarction proved uneconomical. This highlights the need for careful evaluation in future clinical trial designs.
Area of Science:
- Clinical Trials
- Medical Diagnostics
- Health Services Research
Background:
- Central laboratories are often used in multi-center clinical trials to standardize key clinical measurements.
- Variability in local assessments can impact trial outcomes and data integrity.
- The cost-effectiveness and necessity of central laboratory evaluations require careful consideration.
Purpose of the Study:
- To compare central laboratory determinations with local determinations of clinical measurements in three VA Cooperative Studies.
- To assess the cost-effectiveness of central electrocardiogram (ECG) analysis for detecting myocardial infarction.
- To evaluate the impact of central laboratory assessments on the accuracy of local investigators' findings in bypass surgery and angioplasty trials.
Main Methods:
- Analysis of data from three VA Cooperative Studies: Aspirin Therapy and Unstable Angina, Coronary Artery Bypass Surgery Trial, and Angioplasty Compared with Medicine (ACME) Trial.
- Comparison of central laboratory ECG readings with local investigator diagnoses, using a central ECG Committee as the reference standard.
- Assessment of ejection fraction measurements and lesion size by central laboratories versus local investigators.
Main Results:
- Central ECG coding for myocardial infarction detection was not cost-effective compared to local diagnosis in the Aspirin Trial.
- Central laboratories were crucial in the Bypass Surgery Trial, as local assessments underestimated abnormalities.
- Central laboratories were vital in the ACME Trial, correcting local overestimations of lesion severity.
Conclusions:
- Central laboratory evaluations are not universally cost-effective or necessary in all clinical trials.
- The decision to use central laboratories should be based on specific trial needs and potential impact on data accuracy.
- Findings suggest a need for evaluating the contribution of central laboratories to guide future clinical trial design and resource allocation.
Abstract:
We compared central laboratory with local determinations of key clinical measurements in three VA Cooperative Studies. Electrocardiographic evidence of new myocardial infarction was assessed in the study of Aspirin Therapy and Unstable Angina, ejection fraction measurement in the Coronary Artery Bypass Surgery Trial and lesion size in the Angioplasty Compared with Medicine (ACME) Trial. The findings in the Aspirin Trial indicated that central coding of all serial electrocardiograms in 1266 patients to detect new acute myocardial infarction by computer algorithm was not cost-effective when compared with the local investigator's diagnosis on the basis of a central Electrocardiographic Committee as the reference standard. In the other two trials, the contribution of the central laboratories was important because the assessments of the local investigators generally underestimated the degree of abnormality in the Bypass Trial and overestimated it in the ACME Trial. The VA results have clearly demonstrated two cases in which the decision for central evaluation was prudent, but one case in which it was not cost-effective. These equivocal findings indicate the need to evaluate the contribution of central laboratories when used as an adjunct to local determinations. Such evaluations may provide guidelines for decision-making in the design of future trials.