“The cause of the increased mortality and the reason that intervention patients did not initiate treatment sooner could not be identified with available data,” note the authors of the report in the May 15 issue of the Annals of Internal Medicine.
They explain that comprehensive care management programs generally reduce health care use. They hypothesized that a program of patient education, individualized treatment plans for worsening symptoms, and telephone case management would reduce the risk of COPD-related hospitalization.
To test this, Dr. Vincent S. Fan, with the Veterans Affairs Puget Sound Health Care System in Seattle, Washington, and colleagues at twenty VA centers recruited 426 patients who had been hospitalized for COPD in the previous year. The team randomly assigned 209 to the comprehensive care program and 217 to receive standard guideline-based care.
After a mean follow-up of 250 days, the data monitoring committee stopped the trial when 28 deaths from any cause were observed in the intervention group compared to 10 in the usual care arm (hazard ratio 3.00; p=0.003), according to the report.
“Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60; p= 0.053),” the researchers found.
Up to the point the trial was stopped, cumulative 1-year rates of COPD-related hospitalization in the two groups were not significantly different at 27% versus 24% (hazard ratio 1.13; p=0.62).
Dr. Fan and colleagues speculate that patients in the intervention arm may have delayed seeking care for a serious exacerbation because of a false sense of security based on self-treatment per their management plan. However, this could not be verified.
Whatever the reason for the outcome, the authors conclude, “Not all educational and care management programs are appropriate for all patients.”
And they add, “Safety monitoring boards are important for educational and behavioral intervention studies.”
That point is reinforced by the author of an accompanying editorial: “This reminds us all that trials of behavioral strategies are no different from drug trials in their need for effective data monitoring for potential harm, even though some might argue that behavioral actions cannot conceivably harm patients.”
Having said that, Dr. Stuart J. Pocock, of the London School of Hygiene & Tropical Medicine, UK, wonders if the excess deaths in this study represented a random high at the point of termination, and whether mortality rates would have evened out if the trial had continued.
Since that can never be known, he suggests, “It may be best to think of this trial as having stopped for futility — there was no hint of any beneficial effect on the primary outcome.”