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Science is simply common sense at its best, that is, rigidly accurate in observation, and merciless to fallacy in logic.
Thomas Henry Huxley
As the stroke community is invigorated by the recent results of the four trials showing the overwhelming efficacy of endovascular therapy for large vessel occlusion,1–4 we should reflect upon lessons that were learned that may help future clinical initiatives. It has been almost 16 years since the PROACT-II trial showed a 15% absolute difference in outcomes in patients treated with intra-arterial pro-urokinase for a middle cerebral artery (MCA) occlusion compared with medical therapy.5 Although the trial did not compare an endovascular approach with intravenous tissue plasminogen activator (t-PA), we must acknowledge that the journey from the presentation of PROACT-II (ironically at the International Stroke Conference in 1999 in Nashville also) to today has been arduous and protracted.
I would like to share a story of a patient I treated last year, prior to the recent data. A patient of roughly the same age and features as my father came in to our emergency room. The patient had a witnessed event and arrived within 1 h of symptom onset with a right gaze preference and left-sided hemiplegia. We rapidly delivered intravenous t-PA and noted a hyperdense right carotid terminus-M1 MCA sign. I thought through how I was going to ask the family to consent to the participation of the patient in a randomized trial. At that time we had the IMS-III data6 showing no safety concerns with older technologies and hints of efficacy in a subgroup analysis of patients with confirmed large vessel occlusion. Simultaneously, adjudicated head-to-head trials confirmed the superiority of stent retrievers over the older Merci technology with regard to reperfusion and outcomes.7 ,8 Lastly, patients with carotid terminus occlusions were known to have low reperfusion rates with systemic thrombolysis.9 As I worked through the logical argument in my mind, I questioned whether I truly wanted to randomize my patient into a clinical trial. The only justification I could come up with was that the stroke community felt the data were needed as future patients may be harmed without them. I truly saw my father in that bed, but I had a discussion with the patient's family nonetheless. They asked me what I would do if it was my relative and I said I would treat him with endovascular therapy. Many would criticize me for my answer to the family and I respect their viewpoint but, even in retrospect, I do not doubt I guided them in the right direction. I felt my responsibility was to present the data fairly in the consent process and, if they wanted my educated guess as to what to do, I feel I provided them with the guidance I would have given my relative.
When I and the more than 1000 patients randomized in the four clinical trials that have been presented or published look at the sequence of events that have occurred since IMS-III, the question that we should perhaps ask is if the randomized controlled process is necessary for every scientific question. The trials showed such a profound impact of treatment with a composite number needed to treat of one in five, and randomized 549 patients to medical therapy of which only 143 (26%) had a modified Rankin Scale (mRS) score of 0–2.1–4 If they had been treated with endovascular treatment, it is estimated that an additional 113 patients would have achieved a mRS score of 0–2. Although we do not see the faces of these patients and they are a statistic in a journal, it should make us pause to think about how we impacted the lives of these individuals as well as those not in the studies. By no means do I wish to disparage the randomized controlled trial process but, given the magnitude of effect that was found and the logical flow of data that preceded it, we should be more critical of this process and work towards innovative strategies to find answers to looming questions, particularly questions that are evolving faster than a trial can be conducted.
My patient is back working full time at a high level position and is extremely thankful for the care he received. Each time I see him I wonder what would have happened had he been randomized to medical therapy and the impact it would have had on the lives of his children and wife. It was a truly humbling experience, and makes me think that we should be more rigorous in determining which randomized clinical trials to participate in at our institutions. The exuberance that has been generated will also hopefully lead to a strong collective message from the stroke community to healthcare providers and patients regarding the importance of ensuring that appropriate patients are afforded the opportunity to be treated with endovascular stroke therapies.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.