1 Potential Opportunity for a New Device Based Treatment for Migraine Initial results Presented to: Mr. Gill, Jagjit Mr. Khalid Ishaque Boston Scientific Inc. January 2005

2 General  There do not appear to be many significant regulatory barriers beyond the EU Medical Devices Directive affecting ONS for migraine provided that the technology is backed up by good clinical data.  Comparable devices such as those used for neurostimulation for incontinence and epilepsy have received approval from NICE and are in use. NICE evaluation of SCS will begin in April/May  Reimbursement has been made available for neurostimulation for Parkinson’s disease in Germany (funding for SCS is being investigated by HBS). According to the German Medical Technology Association (BVMeD) spinal cord stimulation has been shown to be cost effective for chronic pain. The NHS funds neurostimulation for epilepsy and incontinence. In France, neurostimulation devices are reimbursed (detailed information is being sought via an interview with the responsible person at the Dept of Social Security).

3 General  The UK has a number of active migraine organisations, one of the most influential of which is BASH. BASH has published guidelines on migraine treatment which are considered by Professor Tfelt-Hansen, President of the International Headache Society, to be the most widely recognised guidelines for patient management.Guidelines have also been published by ANAES in France. In the Netherlands, the Institute of Health Policy and Management, Erasmus University Medical Center Rotterdam have recently published Developing a national continuous quality improvement system for neuromodulation treatment in The Netherlands. Because neuromodulation was not included in the national health insurance system, the Dutch Neuromodulation Group (DNG) developed national standards and a continuous quality improvement (CQI) system for consistency in application of neuromodulation techniques and in the quality of outcomes.

4 General  Alan Mock, VP of Marketing at ANS, reports that the most significant barriers to the adoption of ONS in Europe lie with the attitude of physicians  This view is backed up by research conducted so far in Germany. Prof. Dr. Harke, Spokesperson of the working group on Neuromodulation believes that neuromodulation is not appropriate for migraine because the severity of the condition does not warrant an intervention on this scale. Prof. Schwarz at the Institute for neurology in Leipzig reports that he expects neurostimulation to be more frequently used for epilepsy, chronic back pain and incontinence. He believes that migraine pain may not be considered to be sufficiently severe.  ONS is used off label across Europe and it will be interesting to talk to clinicians to assess the scale of usage  Clinicians will also be able to provide additional information on the barriers that they have faced in getting funding for neuropmodulation devices, for SCS or incontinence for example. Although these devices may be covered by NICE guidelines and may be approved by MHRA in the UK, for example, individual trusts may not agree to purchase such devices

5 General: other technologies  ANS has been contacted and interviewed  Interviews with Medtronic scheduled for this week  HBS is also researching the experiences of Neurocor, a Spanish company involved in Neuromodulation which ceased trading  In Germany, Walter Paulas at the University of Gottingen is developing a stimulation device for migraine and chronic headache. (an interview with Pr. Paulas is being sought)  HBS is also researching and seeking interviews with Guidant and Johnson and Johnsion following the recent acquisition of Guidant. Part of the reason given for the acquisition was J&J’s plan to develop technologies in new markets, including neuromodulation