damned if you do and damned if you don’t
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European Journal of Vascular and Endovascular Surgery 43 (2012) 114–115
Contents lists available
European Journal of Vascular and Endovascular Surgery
journal homepage: www.ejves.com
Editorial
Damned If You Do and Damned If You Don’t
“These patients say they cannot afford to wait for research resultsbecause they will wind up in wheelchairs before the studies aredone. Their only option, so far, has been a lifelong course of drugswith limited benefits and harsh side-effects. To some, balloontreatment seems no riskier than those drugs”Denise Grady, New York Times1
In the two years since Zamboni2 proposed that chronic cerebro-spinal venous insufficiency (CCSVI) secondary to stenosis or occlu-sion of the internal jugular or azygous veins might be a treatablecause of multiple sclerosis (MS), the subject has become one ofthe most controversial in medicine. A Google search for CCSVIyielded no fewer than 178,000 hits, mostly representing advertsfor private interventions, internet blogs, pressure groups and Face-book pages, relentlessly exposing the vulnerability, anger anddeeply held frustrations of MS patients.1,3 As far as they are con-cerned, they have little to lose. Research, the medical professionand MS charities have completely failed them. According to Chafe(in a provocative commentary in the journal Nature),3 somepatients have even accused the MS Society and MS Physicians “ofbeing swayed by conflicts of interest because when treatment of CCSVIis introduced, the number of MS patients will drop”. Not surprisingly,therefore, the emerging vox populi message seems to be that theavailable (albeit anecdotal) evidence is believed by many MSpatients to support venoplasty; that randomised trials will taketoo long (as well as being unnecessary) and that many would behappy to consent to a procedure that is perceived to have fewerside-effects than the medications they currently take, even if thebenefits only last for a short period of time.
Conversely, the very mention of CCSVI elicits polarised opinionswithin the medical profession; not least because of the pervasiveemail campaign through which ‘faceless’ lobbyists urge doctors tobe more vigorous in their support of venoplasty in MS patients.At one extreme, private clinics advertise on the internet to vulner-able patients and offer tantalisingly good patient testimonials,whilst espousing the benefits (and safety) of venoplasty. One oftquoted justification is that venoplasty is an accepted interventionalstrategy for other central venous pathologies that have not beensubjected to randomised comparison, sowhy should it be restrictedin MS patients? There have been only two recorded venoplastyrelated deaths,4,5 but Vascular Units are now beginning to reportnew types of complication in patients who have travelled to othercountries to be treated,6 primarily because the procedure is bannedin their own.
At the other extreme, opponents of the move towards unregu-lated venoplasty cite the lack of quality evidence that CCSVI actually
1078-5884/$ – see front matter � 2011 European Society for Vascular Surgery. Publishedoi:10.1016/j.ejvs.2011.10.020
exists and that those performing venoplasty are (in effect) exploit-ing vulnerable patients. Most believe that it is, therefore, unethicalto perform randomised trials because no-one has conclusivelyproved that CCSVI is a proven cause of MS.
It is also true that relatively few studies have been able to repli-cate Zamboni’s original findings (which reported a near unprece-dented 100% specificity and sensitivity),2 although some have, atleast, partially corroborated the CCSVI theory.7 However, a PubMedreview of research papers published in 2011 only identified one(albeit quite large) study that broadly supported the CCSVIhypothesis,7 whilst six other studies did not.8–13 The lack ofconclusive evidence supporting the CCSVI hypothesis has led theCardiovascular and Interventional Radiological Society of Europe(CIRSE) to advise against venoplasty in MS patients,14 while otherregulatory and professional bodies recommend that it should notbe considered outwith properly conducted and ethically approvedresearch trials.15,16 However, in a commentary in the journalNature, Chafe suggests that while “the dominant paradigm is thatan interventional trial is not justified unless there is a strong biologicrationale”, it may be that “in today’s era of ‘Facebook equipoise’, itmay make sense in rare cases to conduct a clinical trial before thedesired weight of scientific evidence is available”.3 He concludedthat; “if the results (of observational studies) are delayed or areunconvincing to many patients, we believe that the benefits ofa double-blinded randomized trial would outweigh the costs,including the diversion of resources from other priorities”. Thisclearly represents a very radical change in the way trials areundertaken and is perhaps indicative of the future power of the‘social media’ to influence practice.
The strength of these contradictory opinions is also apparentwithin the current issue of the European Journal of Vascular andEndovascular Surgery which includes the results of a pilot studyfrom Zamboni et al.17 Although under-powered, he suggests thatimmediate therapy with venoplasty (whilst associated with a 27%restenosis rate), was associated with a significant reduction inannualized relapse rates (compared to patients receiving veno-plasty after 6 months of medical therapy) as well as a trend towardsfewer T2 lesions on MRI in patients undergoing immediate treat-ment. Given the history of this debate, the Editors felt it appropriateto commission a wide variety of commentaries to accompany thispaper. As will be seen, the opinions of our commentators trulyreflect the polarised opinions of Society as awhole. Some are highlycritical, whilst one is supportive. One important message, however,might be the potential role of blindedMRI analysis of the number ofnew T2 lesions as being an objective means of evaluating outcomesin any future randomised trials.
d by Elsevier Ltd. All rights reserved.
Editorial / European Journal of Vascular and Endovascular Surgery 43 (2012) 114–115 115
In order to resolve the current impasse (as well as assuaging thedoubts of MS patients that politicians and doctors don’t care), theCanadian Government has recently agreed to fund $2.4 milliontowards a series of studies relating to CCSVI,18 while in the UK;NICE has called for research (preferably including a sham interven-tion arm) to be undertaken as a matter of priority.15 To-date,however, only two studies in the world are recruiting into a rando-mised trial evaluating venoplasty against sham intervention thatare currently registered with Clinicaltrials.gov. Interestingly, bothof these studies are based at Albany, New York (Clinicaltrials.govIdentifiers: NCT01089686 and NCT01201707). Given the potentialproblems with recruiting desperate and anxious MS patients(who really only want to undergo venoplasty), it might prove diffi-cult to recruit enough patients to complete both studies. Accord-ingly, it does seem somewhat unfortunate that they cannotcollaborate within one protocol.
Notwithstanding the grave concerns held by those who areopposed to performing venoplasty inMS patients, the Editors agreethat it is important that ‘evidence based practice’ rather than ‘Face-book based practice’ determines how we should treat MS patientsin the future. To paraphrase Robert Fox and Alex Rae-Grant; “Itbehoves the clinical research community to carefully pursue CCSVI toits end. We should neither jump on the bandwagon as it passesthrough town, nor assiduously miss the parade”.19
Conflict of Interest
None.
References
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15 http://www.guidance.nice.org.uk/IP/891/DraftGuidance. [accessed 16.10.11].16 http://www.mssociety.org.uk/ms-news-and-research/ms-research/new-and-
potential-treatments/other-avenues-research/ccsvi. [accessed 16.10.11].17 Zamboni P, Galeotti R, Weinstock-Guttman B, Kennedy C, Salvi F, Zivadinov R.
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19 Fox RJ, Rae-Grant A. Chronic cerebrospinal venous insufficiency. Have we foundthe cause and cure of MS? Neurology 2011;77:98–100.
J.-B. RiccoUniversity Hospital, Poitiers, France
A.R. Naylor*Department of Vascular Surgery, Clinical Sciences Building, Leicester
Royal Infirmary, Leicester, UK
* Corresponding author. Tel.: þ44 116 2523252;fax þ44 116 2523179.
E-mail address: [email protected]