Is cerebrovascular neurosurgery sacrificed on the altar of RCTs?
2014; Elsevier BV; Volume: 384; Issue: 9937 Linguagem: Inglês
10.1016/s0140-6736(14)61109-0
ISSN1474-547X
AutoresMiikka Korja, Juha Hernesniemi, Michael T. Lawton, Robert F. Spetzler, M. Morgan,
Tópico(s)Cerebrovascular and Carotid Artery Diseases
ResumoMicroneurosurgery is decreasingly considered a treatment option for people with surgically curable cerebrovascular diseases, partly due to the misconceptions and misinterpretations of some randomised controlled trials (RCTs).1The EC/IC Bypass Study GroupFailure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke.N Engl J Med. 1985; 313: 1191-1200Crossref PubMed Scopus (1612) Google Scholar, 2Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar, 3Molyneux A Kerr R Stratton I et al.for the International Subarachnoid Aneurysm Trial (ISAT) Collaborative GroupInternational Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.Lancet. 2002; 360: 1267-1274Summary Full Text Full Text PDF PubMed Scopus (2919) Google Scholar RCTs are regarded as the gold standard to assess the efficacy of a novel pharmacological intervention. RCTs of drugs do not usually need to focus on the variability in the delivery of care, and ineligible patients are never treated with the study drug outside the RCT on the basis of a clinical decision. However, in the most important RCTs of neurosurgically curable cerebrovascular diseases,1The EC/IC Bypass Study GroupFailure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke.N Engl J Med. 1985; 313: 1191-1200Crossref PubMed Scopus (1612) Google Scholar, 2Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar, 3Molyneux A Kerr R Stratton I et al.for the International Subarachnoid Aneurysm Trial (ISAT) Collaborative GroupInternational Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.Lancet. 2002; 360: 1267-1274Summary Full Text Full Text PDF PubMed Scopus (2919) Google Scholar a substantial number of patients were not randomised but treated in study centres (table). This raises the question of the genuine uncertainty—clinical equipoise—needed to be clarified with an RCT for a small proportion of all patients.TableSelected RCTs in cerebrovascular neurosurgeryCentresCountriesEnrolment (year)End of follow-up (year)PatientsRandomised to surgeryPatients treated outside the trial in study centres*The minimum number of patients treated outside the RCT in the trial centres during the enrolment is estimated on the basis of the reported data in the aricles.2–4 RCT=randomised controlled trial.Patients randomised per centre per year (average)Average follow-up (years)Extracranial-intracranial bypass1The EC/IC Bypass Study GroupFailure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke.N Engl J Med. 1985; 313: 1191-1200Crossref PubMed Scopus (1612) Google Scholar71121977–8219851377663≥19004Goldring S Zervas N Langfitt T The Extracranial-Intracranial Bypass Study. A report of the committee appointed by the American Association of Neurological Surgeons to examine the study.N Engl J Med. 1987; 316: 817-820Crossref PubMed Scopus (85) Google Scholar44·7Ruptured intracranial aneurysms3Molyneux A Kerr R Stratton I et al.for the International Subarachnoid Aneurysm Trial (ISAT) Collaborative GroupInternational Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.Lancet. 2002; 360: 1267-1274Summary Full Text Full Text PDF PubMed Scopus (2919) Google Scholar43101997–2002200221431070≥74163Molyneux A Kerr R Stratton I et al.for the International Subarachnoid Aneurysm Trial (ISAT) Collaborative GroupInternational Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.Lancet. 2002; 360: 1267-1274Summary Full Text Full Text PDF PubMed Scopus (2919) Google Scholar91Unruptured arteriovenous malformations2Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar3992007–1320132265≥11702Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar12·8Data are number unless otherwise specified.* The minimum number of patients treated outside the RCT in the trial centres during the enrolment is estimated on the basis of the reported data in the aricles.2Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar, 3Molyneux A Kerr R Stratton I et al.for the International Subarachnoid Aneurysm Trial (ISAT) Collaborative GroupInternational Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial.Lancet. 2002; 360: 1267-1274Summary Full Text Full Text PDF PubMed Scopus (2919) Google Scholar, 4Goldring S Zervas N Langfitt T The Extracranial-Intracranial Bypass Study. A report of the committee appointed by the American Association of Neurological Surgeons to examine the study.N Engl J Med. 1987; 316: 817-820Crossref PubMed Scopus (85) Google Scholar RCT=randomised controlled trial. Open table in a new tab Data are number unless otherwise specified. In 2013, an RCT of patients with unruptured brain arteriovenous malformations concluded that conservative management was superior to any intervention.2Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar This conclusion has been extrapolated to include treatment by microneurosurgery, despite the fact that of the 114 intention-to-treat patients only 4% were treated with microneurosurgery alone and 11% had surgery as part of their multimodality treatment. Moreover, more than 80% of patients were treated outside the trial, and, on average, only one patient per centre per year was randomised. The conclusion to be drawn on the basis of this study2Mohr JP Parides MK Stapf C et al.for the International ARUBA investigatorsMedical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.Lancet. 2013; 383: 614-621Summary Full Text Full Text PDF PubMed Scopus (890) Google Scholar is that decision-making processes in participating centres are opaque and the treatment results of the study might not be applied to all unruptured brain arteriovenous malformations. With our experience in cerebrovascular surgery (ie, more than 1750 operated brain arteriovenous malformations), we believe that not only demanding cerebrovascular operations but also treatment decisions should be centralised in high-volume cerebrovascular centres. The next RCT of a surgically curable, fairly rare, and potentially life-threatening cerebrovascular disease should perhaps start with defining and establishing the best treatment centres and neurosurgeons along with highly objective, reliable, and accepted quality-of-care measures. Then, the RCT could proceed with randomisation of all patients to treatment groups if this is possible for such immediate high-stakes outcomes. The aim of the RCT would be to define the best treatment option in high-volume treatment centres for all patients with fairly rare and potentially life-threatening cerebrovascular disorders, and not to extrapolate unsatisfactory treatment strategies from a small and undefined proportion of treated patients. We thank Gillian Heller (Department of Statistics, Macquarie University, Sydney, Australia). We declare no competing interests.
Referência(s)