Of late the New England Journal of Medicine has seemed like the burial ground of good ideas. Researchers follow a promising lead only to find that their new idea fails the crucial test of experience: and the difference between success and failure in research is made to appear as much a matter of chance or luck as of brilliance or skill.
In the first issue of the Journal for 2015, Dutch researchers from 16 different hospitals report an unequivocal success in the treatment of ischemic stroke.
Until now the only proven worthwhile treatment of patients with the kind of stroke that results from the blockage of a cerebral artery is the infusion within four and a half hours of the drug called alteplase, which dissolves thrombus (and which is manufactured from the ovaries of Chinese hamsters). But even with the use of this drug the prognosis is not very good, and there are several contra-indications to its use.
If a blood clot is at the origin of a stroke, causing the death of the cerebral tissue served by the artery in which the clot takes place, it seems to stand to reason that physical removal of the clot as soon as possible after it formed would improve the outcome. Of course, this is not easy, and trials of the technique using stents have hitherto not been successful. But the Dutch researchers, using the latest stent, showed that they could improve the prognosis by this technique.
They conducted a trial in which they assigned 500 patients with stroke caused by blockage of the anterior cerebral artery at random either to normal treatment (which included the use of alteplase), or to attempted removal of the clot by stent. It took them 3 years to find 500 patients who met the criteria for the trial.
They measured the outcome by a number of criteria, including the proportion of patients who returned to independent functioning after treatment, as well as radiographic measurement of the size of the area of brain damaged after the original stroke. The results were gratifyingly favorable. They were not just statistically significant, but clinically significant, too: in other words, the patients and not just the researchers actually benefited from the treatment. For example, 19.5 percent of patients who receive only normal treatment returned to independent functioning, whereas 32.6 percent of those treated by stent did so. These findings were supported by the radiographic evidence. In other words, you would have to treat about eight patients with this kind of stroke to have an extra patient return to independent functioning.
The authors are careful not to sound triumphant and to point out the limitations of their experiment. Like any successful experiment done for the first time and only once, it must be repeated. And there were various other caveats, too, such as that the patients themselves knew to which arm, experiment or control, they had been assigned, and this might have affected the outcome, at least as far as their self-assessment was concerned. But the caveats were not serious enough to undermine the success of the trial.
One little phrase caught my attention.
The doctors who took part in the trial had to have performed the stenting procedure using the latest technology and appliances at least five times before they were allowed to participate in it. This meant that many procedures must have been performed previously without knowing whether or not they would benefit the patients. From the point of view of current rigorous medical ethics, those procedures were probably unethical, though not of course meant maliciously. Perhaps there is an inevitable tension between medical advance and medical ethics.