Thursday, February 08, 2007

The CAST trial: EBM and unexpected answers

The Houston Chronicle has started a new medicine column, and the first installment, "Evidence is key when it comes to your treatment by Dr. Howard Brody, discusses what evidence-based medicine means to the patient.

Dr. Brody uses very accessible, everyday language - he briefly describes the CAST trial, a large study with initial results published in 1990 - this study looked at drugs for suppressing a type of irregular heart beat, premature ventricular contractions (PVCs) and was terminated due to an interim analysis (a planned safety monitoring analysis conducted partway through the study) that indicate that drug therapy was actually associated with increased mortality, rather than reduced number of deaths as had been expected.

Dr. Brody summarizes the study:

So, allow me to tell you a story that goes back to 1989.

Scientists knew two things back then. First, older people who had a certain kind of irregular heartbeat were much more likely to die of coronary disease. Second, a class of drugs was very good at reducing the number of irregular beats.

So they designed a big research study, called CAST, to see whether giving those drugs to older, at-risk people saved lives.

Some would have said, "Why even bother to do the trial? You can already tell in advance these drugs will be a good thing. Why not just go ahead and prescribe them?"

CAST gave a clear-cut answer, all right, but it was the opposite of what everyone expected. They had to stop the study early because so many people getting the drugs were dying prematurely.
He further sums up how this illustrates EBM:

Some people beat up on EBM because they imagine it is just one more excuse for cutting costs...the more important use is to save people from worthless or harmful treatment. Imagine how many extra deaths would have occurred, had those heart-rhythm drugs studied in CAST been released for wide use...If you go to a good physician, it's very likely she thinks in EBM terms. If you know more about what she's thinking, you can get more involved in your own medical care and know a lot better what sorts of questions to ask. And more-involved patients stay healthier. The evidence shows it.
Additional information:
- the PubMed abstract for one of the initial reports of the unexpected mortality
- a broader PubMed search of articles reacting to this study, which is still being talked about today

- It's also worth noting that, though the study did not succeed in proving its primary hypothesis, that drug therapy to suppress PVCs would decrease the death rate in treated patients, it did lead to the creation of a rich dataset that has spawned numerous studies published since then, represented in the above PubMed search and the ClinicalTrials.gov description of CAST (this record also has a list of studies that were based on this dataset, which is still maintained by the study investigators and available to other researchers for further analyses, managed by the National Heart, Lung, and Blood Institute.

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