November 23, 2017


Combating the Spread of Ineffective Medical Procedures : A Lesson Learned From Multiple Sclerosis (Ari J. Green, MD, MAS1,2,3,4; Hooman Kamel, MD4,5,6; S. Andrew Josephson, MD1,2,7, 11/17, JAMA Neurol. )

The Information Age has had a staggering effect on the spread and democratization of knowledge. The increased availability of cutting-edge data has accelerated the speed of breakthroughs. Faster communication of major discoveries in science has highlighted the need for scientists and physicians to hone their skills at simple and clear communication of their newfound knowledge to the general public. In medicine, we have realized significant gains by broadening international collaboration and widening the audience for medical knowledge.

However, these advances have come at a cost. The value of expertise has at times been degraded, and the careful judicious review of data has sometimes been compromised in the effort to quickly circulate new findings to the largest possible audience. At times, preliminary concepts that might have previously helped catalyze new thinking--but that still should have been considered provisional--have been inappropriately regarded as signaling a paradigm shift, without the requisite opportunity for expert appraisal. This is an important danger that we need to address.

In 2009, Zamboni et al concurrently published 2 studies1,2 on venous stasis in multiple sclerosis (MS). As part of this work, Paolo Zamboni, MD, coined the term chronic cerebrospinal venous insufficiency (CCSVI) to describe a phenomena of hypoplasia, intraluminal defects in the internal jugular and azygous veins, and an ill-defined concept that he termed compression. The first study1 described the CCSVI pattern and reported an extraordinarily high frequency of CCSVI findings in patients with all types of MS, with greater than 70% of patients harboring different CCSVI features (compared with 0% to 11% of controls). Zamboni et al1 also reported that patients with MS had a more than an 1100-fold increase in the odds of having reflux in their internal jugular or vertebral veins. A sister publication2 described the observed benefits of an open-label study for percutaneous balloon venoplasty in patients with MS with identified CCSVI. These publications together suggested that the field had overlooked the possibility that venous pooling in the central nervous system contributed to the pathogenesis of MS. Zamboni, who had begun his foray into MS research as an established expert in vascular disease and treatment, freely acknowledged in later press coverage that the experience his wife had with MS helped motivate him to help to do something transformational. [...]

In this issue of JAMA Neurology, Zamboni and colleagues12 report the results of their definitive randomized, double-blind sham-controlled clinical trial. This trial of 115 participants (of whom 76 were randomized to receive percutaneous transluminal venous angioplasty and 39 to receive a sham procedure) finds no benefit for "liberation treatment" for patients with MS, including no benefit in a disability outcome measure that included assessments of walking, balance, hand function, urinary function, and visual acuity. No benefit was seen for treated patients with regards to the percentage of patients who were free of new lesions or the number of new brain lesions observed. The disability outcome measure was novel and not the typical Expanded Disability Status Score or Multiple Sclerosis Functional Composite score, but this option was intentionally chosen by the investigators out of concern that the standard measures of disability would be insensitive to possible benefits. The study was smaller than initially intended, but the results suggested absolutely no benefit to treatment, with the primary end point actually favoring the sham procedure. [...]

As clinicians, we owe it to patients to protect them from false advances without appropriate efficacy and safety data, but we are often confronted with a wave of pressure from referring physicians, hospitals, advocacy groups, and the patients themselves. Zamboni et al should be applauded for their clear-eyed evaluation12 of their earlier theory1,2 in a rigorous and definitive fashion. It is difficult to refute one's own prior findings, but the authors have used the right methods to test the CCSVI theory and have yielded an unequivocal result.

We have an epidemic in medicine of these types of stories. As with infectious disease outbreaks, we can best learn how to control spread of ill-advised communicable ideas by reviewing what went wrong in the last occurrence. Hopefully, the field can use this lesson to identify what can be done to inoculate ourselves against similar future events.

Posted by at November 23, 2017 5:31 AM