Could the RATPAC trial have been stopped earlier with a different design?

The RATPAC trial [1] showed that using a point of care panel of troponin, CK-MB and myoglobin at presentation and 90 minutes could increase the proportion of patients successfully discharged after emergency department assessment for non-specific chest pain. The trial originally planned to recruit 3130 participants. After a lot of hard work and an extension to the planned time, the trial stopped with 2243 patients recruited after an interim analysis showed that further recruitment was unlikely to add worthwhile new information.

A reanalysis of the RATPAC trial data, published in the October issue of Annals of Emergency Medicine [2], suggests that the trial could have been stopped a year earlier, after 722 patients had been recruited, if a group sequential design had been used. This is a type of adaptive design which allows a trial to be stopped prematurely because of efficacy, futility or safety, according to the results of pre-planned interim analyses.

The reanalysis and an accompanying editorial [3] suggest that adaptive designs could be used more widely in emergency medicine to allow early recognition of an effective intervention or early termination of a futile trial. There are potential drawbacks to an adaptive design, however. Early termination of the RATPAC trial would have left it with less power to detect differences in secondary outcomes, such as adverse events and health care costs. This could be a problem as the RATPAC economic analysis [4] showed that, despite reducing admissions, use of the point of care panel may have been associated with increased health care costs.

Steve Goodacre

1. Goodacre SW, Bradburn M, Cross E, Collinson PO, Gray A, Hall AS on behalf of the RATPAC research team. The RATPAC Trial(Randomised Assessment of Treatment using Panel Assay of Cardiac markers): Arandomised controlled trial of point-of-care cardiac markers in the emergencydepartment. Heart 2011;97:190-196.
   
2.  Sutton L, Julious S, Goodacre S. Impact ofAdaptive Analysis on Unnecessary Patient Recruitment: Re-Analysis of the RATPACTrial. Ann Emerg Med 2012;60:442-448.
    
3.  Durkalski V. Adaptive designs: A true panaceafor the common clinical trial? Ann Emerg Med 2012;60:449-450.
    
4.  Fitzgerald P, Goodacre SW, Cross E, Dixon S. Cost-effectiveness of point-of-care biomarker assessment for suspectedmyocardial infarction: The RATPAC Trial (Randomised Assessment of Treatmentusing Panel Assay of Cardiac markers). Acad Emerg Med 2011;18:488-495.