At the end of this post, I’ll tell you why I care.
Last week there was an eruption in the cardiology world. The NIH funded ISCHEMIA trial was designed in 2011 to definitively answer if coronary artery stenting in non-acute situations significantly prevents heart attacks or cardiac death. Over 10 years ago, the COURAGE trial was published in the New England Journal of Medicine. It found no clinical benefit from stenting over optimal medical therapy. Their conclusion was “as an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy.” (N Engl J Med 2007; 356:1503-1516)
The ISCHEMIA trial was designed with harder primary endpoints (cardiovascular death or heart attack). It was designed to provide a definitive answer to this question and to avoid the softer endpoints included in COURAGE. The trial would be expensive and lengthy. It would require 8000 patients and many years of work. They anticipated the study to be fully enrolled within a few years and to have their primary endpoints complete in May 2018. But after over six years of toil by these researchers, only 5000 patients had been enrolled into this important study. And they were nowhere near the number of endpoints needed to be collected.
So what did the lead investigators do? They widened the primary endpoints of the study. They added hospitalization for unstable angina or heart failure as primary endpoints. By doing so, they could salvage the ability to publish some meaningful data rather than risking losing all of this work due to loss of funding as the cost of this trial spiraled upward. They didn’t do anything unethical. They had built this contingency into the research protocol all those years earlier. But why did they do it?
They didn’t do it because they wanted to. They did it because they had to. And they had to because too few physicians and patients were participating. About 735,000 Americans have heart attacks every year and about 610,000 Americans die each year from heart disease. (https://www.cdc.gov/heartdisease/facts.htm) One year! Well over 1 million unique events. But in over seven years of working on this important research, these investigators only found 5000 patients. That’s why I care. That’s why this is important. Because, honestly, it’s not just this trial. It’s all research. Research costs what it does and therefore therapies are priced as they are because of this. Because of the inefficiency. Because of the lack of participation. If we can fix this, we can massively impact research pricing and therefore healthcare costs. Oh, we can also get new therapies to the patients that need them quicker.
Full article: https://www.forbes.com/sites/larryhusten/2018/03/18/cardiology-world-erupts-into-controversy-over-change-in-major-clinical-trial/#533e4e5151f5
COURAGE trial: https://www.nejm.org/doi/full/10.1056/NEJMoa070829
ISCHEMIA trial: https://clinicaltrials.gov/ct2/show/NCT01471522