Experiences with Sacral Neuromodulation for Urinary Control and Bowel Control

Agenda Prevalence & Impact of Overactive Bladder Prevalence & Impact of Chronic Fecal Incontinence InterStim Therapy for Urinary Control and Bowel Control Efficacy & Safety Information Test Procedure & System Overview Medtronic Support Q&A

Overactive Bladder: Prevalence & Impact OAB1 Asthma2 Diabetes3 Osteoporosis4 Alzheimer’s5 It is estimated that overactive bladder (OAB) affects more than 33 million people in the U.S.1 OAB is more prevalent than many well-known diseases.2-5 The total U.S. economic cost of OAB is $12.6 billion (year 2000 dollars).6 Overactive bladder affects more than 33 million people. As you can see by this picture, it is more prevalent than some other common conditions such as asthma, diabetes, osteoporosis, and Alzheimer’s. The total economic cost was calculated to be more than $12 billion in the US for OAB alone. 1. Serels S. The wet patient: understanding patients with overactive bladder and incontinence. Curr Med Res Opin. 2004;20(6):791-801. 2. Centers for Disease Control and Prevention Website. http://www.cdc.gov/asthma/brfss/03/lifetime/tableL1.htm. Accessed October 18, 2010. 3. National Diabetes Information Clearinghouse Website. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people. Accessed October 18, 2010. 4. National Osteoporosis Foundation Website. http://www.nof.org/node/40. Accessed October 18, 2010. 5. Alzheimer’s Association Website. http://www.alz.org/alzheimers_disease_facts_figures.asp. Accessed October 18, 2010. 6. Hu, TW et al. Costs of Urinary Incontinence and Overactive Bladder in the United States: A Comparative Study. Urology.2004;63(3):461-465.

Patient Survey Data* NAFC survey data found OAB patients seek treatment for the following reasons: Frustration from living with the symptoms (78%) Embarrassment (42%) Physical discomfort (38%) 74% of surveyed OAB patients said they waited longer than they should have to seek treatment Only 20% of surveyed OAB patients are extremely satisfied with their current treatment * Source: Survey for the National Association for Continence (NAFC), sponsored by Medtronic, Inc. and conducted by Kelton Research. April 2009. The online survey was conducted using an email invitation. Respondents were 611 nationally representative American women ages 40-65 with overactive bladder.

Pharmacotherapy Persistence & Adherence OAB medications in the California Medicaid Program1 6- Month Persistence & Adherence 77% 73% 82% > 70% discontinuation of prescribed therapy within 6 months > 80% discontinuation of prescribed therapy within 1 year > 50% chose not to restart their therapy after discontinuation Three major drugs were analyzed in a large retrospective study. 70% of patients discontinued their prescribed therapy within 6 months. More than 50% chose not to restart therapy after discontinuation. 1. Yu YF, Nichol MB, Yu AP, et al. Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the California Medicaid Program. Value in Health. 2005;8(4):495-505.11

Pharmacotherapy Persistence & Adherence OAB medications compared to those for several other chronic conditions OAB Medications Prostaglandins Analogs (indicated for glaucoma) Bisphosphonates (osteoporosis) Statins (hyperlipidemia) ARBs (hypertension) Oral antidiabetics (Type II) Persistent at 6 months Persistent at 1 year Only 28% of patients on OAB medications remained persistent at 6 months Only 18% of patients on OAB medications remained persistent at 1 year Patients were less likely to remain on OAB medications than on any other drug class assessed 1. Yeaw J, Benner JS, Walt JG, Sian S, Smith DB. Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm. 2009;15:724-736.

Fecal Incontinence- More Common Than You Might Think OAB1,2 Asthma3 Diabetes4 FI 5 Osteoporosis6 Alzheimer’s7 It is estimated that more than 18 million adults in the United States – 1 in 12 – suffer from fecal incontinence (FI)5 FI is nearly as prevalent as many other chronic diseases and more prevalent than other illnesses well-known to impact many Americans.1-4,6-7 1. Stewart, W.F et al. Prevalence and Burden of Overactive Bladder in the United States.World Jrnl of Urol 2003:20:327-336 2. Serels S. The wet patient: understanding patients with overactive bladder and incontinence. Curr Med Res Opin. 2004;20(6):791-801. 3. Centers for Disease Control and Prevention Website. http://www.cdc.gov/asthma/brfss/03/lifetime/tableL1.htm. Accessed October 18, 2010. 4. National Diabetes Information Clearinghouse Website. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/#y_people. Accessed October 18, 2010. 5. Whitehead W.E. et al. Fecal Incontinence in US adults: epidemiology and risk factors. Gastroenterology. 2009; 137:512-517. 6. National Osteoporosis Foundation Website. http://www.nof.org/node/40. Accessed October 18, 2010. 7. Alzheimer’s Association Website. http://www.alz.org/alzheimers_disease_facts_figures.asp. Accessed October 18, 2010.

FI Impacts Quality of Life Note: Higher scores translate to higher quality of life FI Impacts Quality of Life Fecal Incontinence Quality of Life Scale (FIQOL) Scores Patients are particularly anxious about the unpredictability of episodes of fecal incontinence and often alter their social and professional activities to avoid embarrassment.(1 ) 1. Wald A. Fecal Incontinence in Adults. New England Journal of Medicine. 2007;356(16):1648-1655. Medtronic data on file. InterStim Therapy for Bowel Control Prospective Clinical Study. PMA#P080025.

Patient Education Needed Studies suggest that only 15%– 45% of FI patients seek treatment1,2. Consider the following statistics that support the claim that fecal incontinence is a hidden condition: For 84% of patients with FI, the physician was unaware of the patient’s disorder1 54% of patients with FI had not discussed the problem with a professional2 65% of patients with severe or major FI which had an impact on the quality of life wanted help with their symptoms3 1. Damon H, Guye O, Seigneurin A, et al. Prevalence of anal incontinence in adults and impact on quality-of-life. Gastroenterol Clin Biol. 2006;30(1):37-43 2. Edwards NI, Jones D. The Prevalence of Faecal Incontinence in Older People Living at Home. Age Ageing. 2001;30(6):503-7 3. Perry S, Shaw C, McGrother C, et al. Prevalence of faecal incontinence in adults aged 40 years or more living in the community. Gut. 2002;50(4):480-484. 

InterStim Therapy for Urinary Control and Bowel Control An established therapy that expands your treatment options for patients with: urge incontinence, urgency-frequency, non-obstructive urinary retention, chronic fecal incontinence who do not benefit from more conservative treatments. More than 100,000 patients worldwide have received InterStim Therapy

InterStim Delivers Clinical Efficacy 12-month clinical success for Urinary Control1 79% of urge incontinence patients achieved clinical success • 45% remained completely dry • An additional 34% experienced 50% reduction in leaking 64% of urgency-frequency patients achieved clinical success Urgency- Frequency (n=33) • 31% returned to normal voids (4 to 7 voids/day) • An additional 33% experienced 50% reduction in number of voids Urge Incontinence (n=38) Urinary Retention (n=38) 77% of urinary retention patients achieved clinical success 1. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011. • 61% eliminated use of catheters • An additional 16% experienced 50% reduction in catheterized urine volume

Lasting Efficacy - Proven in a 5-year Clinical Trial InterStim Therapy for Urinary Control Lasting Efficacy - Proven in a 5-year Clinical Trial Urge Incontinence1 Evaluable Patients – the subset of subjects for whom both baseline and 5-year data were available Intent-to-Treat Patients – all implanted subjects, including those who dropped out and were imputed as no change from baseline 59% of urge incontinent patients achieved  50% reduction in leaks/day* 71% of those urge incontinent patients who reported heavy leaks at baseline achieved  50% reduction in leaks per day† * 59% in evaluable patient population (n=61) and 37% in intent-to-treat population (n=96) † 71% in evaluable patient population (n=49) and 42% in intent-to-treat population (n=84) 1. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011.

Lasting Efficacy - Proven in a 5-year Clinical Trial InterStim Therapy for Urinary Control Lasting Efficacy - Proven in a 5-year Clinical Trial Urgency-Frequency1 Evaluable Patients – the subset of subjects for whom both baseline and 5-year data were available Intent-to-Treat Patients – all implanted subjects, including those who dropped out and were imputed as no change from baseline 56% of urgency-frequency patients achieved 50% increase in volume voided/void and improved degree of urgency* * 56% in evaluable patient population (n=18) and 40% in intent-to-treat population (n=25) 1. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011.

Lasting Efficacy - Proven in a 5-year Clinical Trial InterStim Therapy for Urinary Control Lasting Efficacy - Proven in a 5-year Clinical Trial Urinary Retention1 Evaluable Patients – the subset of subjects for whom both baseline and 5-year data were available Intent-to-Treat Patients – all implanted subjects, including those who dropped out and were imputed as no change from baseline 78% of urinary retention patients achieved  50% reduction in volume/catheterization* * 78% in evaluable patient population (n=23) and 58% in intent-to-treat population (n=31) 1. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011.

Clinical Efficacy: Reduction in Episodes InterStim Therapy for Bowel Control Clinical Efficacy: Reduction in Episodes InterStim Therapy Bowel Control Study 9.4 9.2 Mean Number of Weekly Incontinent Episodes Modified Worst Case (MWC) (n=120) 3.1 Per-protocol analysis: NOTE- aka “Evaluable” (term used in 5yr Uro data) -This analysis was conducted with patients who had complete data at baseline and at annual follow-up visits. Modified Worst Case: This analysis assumed no improvement for patients who were missing bowel diaries (tool used to measure symptom improvement from baseline) at the follow-up visits, unless a subsequent bowel diary was available. Per-protocol (completers) (n=106) 1.9 Baseline 12 Months Baseline 12 Months 1. Wexner SD, Coller JA, et al. Ann Surg. 2010 Mar;251(3):441-9. 2. Medtronic-sponsored research. InterStim Therapy Clinical Summary - 2011.

Clinical Efficacy: Complete Continence InterStim Therapy for Bowel Control Clinical Efficacy: Complete Continence InterStim Therapy Bowel Control Study1,2 Tjandra RCT3 47% 41% 36% Percent of Patients with a 100% Reduction in Accidents at 12 Months Complete Continence = 100% reduction in accidents Modifified worst case analysis (MWC) assumed no change for patients who were lost to follow-up or missing bowel diaries at the 12 month visit. Per-protocol analysis (Completers analysis) was conducted for patients who had complete data both at baseline and at the 12 month visit. Of special note is the fact that in the InterStim Therapy Bowel Control Study per-protocol analysis (n=106), 41% achieved complete continence, while 36% of the 120 patients in the intent-to-treat analysis completing the study achieved complete continence with the help of InterStim Therapy at the 12 month follow-up visit. An intent-to-treat analysis was conducted which assumed no change for patients who were missing bowel diaries at the 12 month visit unless a subsequent bowel diary was available (modified worst-case analysis). Another per-protocol analysis was conducted for patients who had complete data both at baseline and at the 12 month visit (completers analysis) MWC (n=120) Per-protocol (n=106) SNS group (n=53) 1. Wexner SD, Coller JA, et al. Ann Surg. 2010 Mar;251(3):441-9. 2. Medtronic-sponsored research : InterStim Therapy - Clinical Summary, 2011. 3. Tjandra JJ et al. Sacral nerve stimulation is more effective than optimal medical therapy for severe fecal incontinence: a randomized, controlled study. Dis Colon Rectum. May 2008;51(5):494-502.

Clinical Efficacy: Quality of Life InterStim Therapy for Bowel Control Clinical Efficacy: Quality of Life InterStim Therapy Bowel Control Study1 1. Wexner SD, Coller JA, Devroede G, et al. Sacral nerve stimulation for fecal incontinence: results of a 120-patient prospective multicenter study. Ann Surg. Mar 2010;251(3):441-449.

Adverse Events The most common adverse events experienced during clinical studies included: Pain at implant sites New pain Lead migration Infection Technical or device problems Adverse change in bowel or voiding function Undesirable stimulation or sensations Any of these may require additional surgery or cause return of symptoms. For additional safety information, please refer to the Important Safety Information on the last slide of this presentation.

Test for Potential Success Basic Evaluation A temporary lead is placed during a simple in-office procedure and connected to an external stimulator You and your patient assess therapy effects in as few as 3-7 days If successful, patient may proceed directly to long-term lead and device implant through an outpatient procedure If test is inconclusive or unsuccessful, the advance evaluation via the staged test is recommended For the test stimulation, a lead is placed near the sacral nerves, and the patient wears an external, programmable neurostimulator. To assess whether the therapy is successful, the patient records his or her voiding behavior in a diary.

Test for Potential Success Advanced Evaluation Utilizes a tined lead that anchors in place Placed in the OR during an outpatient procedure You and your patient assess therapy effects for up to 14 days With successful test results, the lead remains in place and the device & lead extension (if applicable) are implanted Complications can occur with the test procedure, including movement of the wire, technical problems with the device, and some temporary pain.

Complete InterStim System Tined lead is placed parallel to the sacral (S2, S3, or S4) nerve. Implantable neurostimulator generates mild electrical pulses that are delivered through the lead electrodes. Clinician and patient programmers are used to set the parameters of the electrical pulses. 3 2 2 The InterStim or InterStim II INS. The InterStim II INS is shown with the InterStim Tined Lead Model 3093. The InterStim iCon® patient programmer Model 3037 supports both the InterStim and InterStim II INS devices with identical features. With the Version B clinician programmer software, the N’Vision® clinician programmer can be used to program the InterStim II INS Model 3058 and the InterStim INS. Please note both InterStim II (3058) and InterStim stimulators (3023) are shown, and 3023 requires an extension. 1

The Pelvic Floor S3, the most distal common point of innervation for the bladder InterStim Therapy stimulates S3 or S4

Evaluating for InterStim: Treatment Algorithm InterStim Therapy for Urinary Control Evaluating for InterStim: Treatment Algorithm Urge Incontinence & Urgency-Frequency Initial Screening Voiding Diary Urodynamic Work-up Behavioral Techniques Interventional Techniques Medications - + Continue as Appropriate InterStim Therapy Test Stimulation

Evaluating for InterStim: Treatment Algorithm InterStim Therapy for Urinary Control Evaluating for InterStim: Treatment Algorithm Urinary Retention Initial Screening Voiding Diary Urodynamic Work-up Rule Out Obstruction Medications and/or Catheterization - + Continue as Appropriate InterStim Therapy Test Stimulation

Evaluating for InterStim: Treatment Algorithm InterStim Therapy for Bowel Control Evaluating for InterStim: Treatment Algorithm Fecal Incontinence Initial Evaluation Conservative Treatment Diet Modification Medication Behavioral Therapy InterStim Therapy Test Evaluation - - + + 2nd Test Evaluation InterStim Implant Continue as Appropriate Other Surgical Treatment

InterStim Therapy for Urinary Control Coverage The coverage profile for sacral nerve stimulation is strong: Medicare National Coverage Determination Medicare Local Coverage Determinations (many retired) Most commercial payers have coverage policies in place Common diagnoses include: 788.20 - Retention of urine, unspecified 788.21 - Incomplete bladder emptying 788.29 - Other specified retention of urine 788.31 - Urge incontinence 788.41 - Urinary frequency InterStim Therapy has established physician and facility coding. In terms of the outpatient facility payment method, the Ambulatory Payment Classification system, the devices are covered by the amounts the hospital receives. Specifically for a physician in the office, a payment of $1,068 is received for an in-office (non-facility) percutaneous test. The American Medical Association has recently communicated that when physicians place two percutaneous leads, the second lead is reimbursed at 50%. (All amounts are national averages.) Medtronic provides this information for your convenience only. It is not intended as a recommendation regarding clinical practice. It is always the provider’s responsibility to determine coverage and submit appropriate codes, modifiers, and charges for the services that were rendered. This document provides assistance for FDA approved or cleared indications. Where reimbursement is requested for a use of a product that may be inconsistent with, or not expressly specified in, the FDA cleared or approved labeling (e.g., instructions for use, operator’s manual or package insert) consult with your billing advisors or payers for advice on handling such billing issues. Some payers may have policies that make it inappropriate to submit claims for such items or related service. Contact your Medicare contractor or other payer for interpretation of coverage, coding, and payment policies.

InterStim Therapy for Bowel Control Coverage The coverage profile for sacral nerve stimulation for fecal incontinence is developing: Medicare Local Coverage Determinations (emerging) Many commercial payers have coverage policies in place Diagnosis code used: 787.60 fecal incontinence Same procedural codes (CPTs) used as for urinary control InterStim Therapy has established physician and facility coding. In terms of the outpatient facility payment method, the Ambulatory Payment Classification system, the devices are covered by the amounts the hospital receives. Specifically for a physician in the office, a payment of $1,068 is received for an in-office (non-facility) percutaneous test. The American Medical Association has recently communicated that when physicians place two percutaneous leads, the second lead is reimbursed at 50%. (All amounts are national averages.) Medtronic provides this information for your convenience only. It is not intended as a recommendation regarding clinical practice. It is always the provider’s responsibility to determine coverage and submit appropriate codes, modifiers, and charges for the services that were rendered. This document provides assistance for FDA approved or cleared indications. Where reimbursement is requested for a use of a product that may be inconsistent with, or not expressly specified in, the FDA cleared or approved labeling (e.g., instructions for use, operator’s manual or package insert) consult with your billing advisors or payers for advice on handling such billing issues. Some payers may have policies that make it inappropriate to submit claims for such items or related service. Contact your Medicare contractor or other payer for interpretation of coverage, coding, and payment policies.

Coding: CPT* Unique codes included on the 2010 Medicare Physician Fee Schedule for placement of electrodes on the sacral nerve: CPT 64561: Percutaneous implantation of neurostimulator electrodes; sacral nerve (transforaminal placement) (2010 Medicare Physician Payment National Average: Non Facility Setting: $1,046/Facility Setting: $417) CPT 64581: Incision for implantation of of neurostimulator electrodes; sacral nerve (transforaminal placement) (2010 Medicare Physician Payment National Average: Facility Setting: $826) CPT 64590: Insertion or replacement of peripheral neurostimulator pulse generator or receiver, direct or inductive coupling (2010 Medicare Physician Payment National Average: Facility Setting: $177) CPT 95972: Complex spinal cord or peripheral (except cranial nerve) neurostimulator pulse generator transmitter with intraoperative or subsequent reprogramming, first hour (2010 Medicare Physician Payment National Average: Non Facility Setting: $108/Facility Setting: $79) *CPT is a registered trademark of the American Medical Association. Current Procedural Terminology (CPT) is a copyright 2009 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. Medicare payment is determined by multiplying the sum of the three RVUs (work, practice expense and malpractice) by the conversion factor. The conversion factor for CY 2010 is $36.8729. On June 25, 2010 the President signed into law HR 3962. This provides a 2.2% increase to the Physician Medicare Fee Schedule from June 1, 2010 through November 30, 2010. The bill may be found at: http://www.govtrack.us/congress/bill.xpd?bill=h111-3962. National average Medicare rates are shown here. Also note that any applicable coinsurance, deductible, and other amounts that are patient obligations are included in the payment amount shown. Multiple surgical procedure reductions may apply and are not calculated here. In addition to the outpatient hospital setting, the ambulatory surgery center (ASC) in also a potential setting for tests and implants.

Medtronic Reimbursement Resources Medtronic has resources available to assist your practice with coding and reimbursement considerations: Field Based Health Economics Managers (available for coding and reimbursement education, claims reviews, appeal assistance, meetings with facilities, etc.) Coding Sheets (Procedural and Diagnosis) Financial/Coding Models Dictation Guides Prior Authorization Guides and Sample Letters of Medical Necessity

Additional Resources for Physicians Training & Education Patient Awareness & Education Resources Therapy Integration Consultation

Summary The condition of OAB is common and persistence and adherence with medication therapy is suboptimal Fecal incontinence is a hidden condition that can severely impact quality of life InterStim is an established therapy with proven long-term clinical efficacy A simple test procedure initiated in the office helps determine whether InterStim Therapy may help restore control over symptoms Reimbursement for InterStim is generally favorable Medtronic offers comprehensive support

Important Safety Information InterStim Therapy for Urinary Control is indicated for the treatment of urinary retention and the symptoms of overactive bladder, including urinary urge incontinence and significant symptoms of urgency-frequency alone or in combination, in patients who have failed or could not tolerate more conservative treatments. The following Warning applies only to InterStim Therapy for Urinary Control: Warning: This therapy is not intended for patients with mechanical obstruction such as benign prostatic hypertrophy, cancer, or urethral stricture. InterStim® Therapy for Bowel Control is indicated for the treatment of chronic fecal incontinence in patients who have failed or are not candidates for more conservative treatments. Contraindications for Urinary Control and for Bowel Control: Diathermy. Patients who have not demonstrated an appropriate response to test stimulation or are unable to operate the neurostimulator. Precautions/Adverse Events: For Urinary Control: Safety and effectiveness have not been established for bilateral stimulation; pregnancy, unborn fetus, and delivery; pediatric use under the age of 16; or for patients with neurological disease origins such as multiple sclerosis. For Bowel Control: Safety and effectiveness have not been established for bilateral stimulation; pregnancy, unborn fetus, and delivery; pediatric use under the age of 18; or for patients with progressive, systemic neurological diseases. For Urinary Control and for Bowel Control: The system may be affected by or adversely affect cardiac devices, electrocautery, defibrillators, ultrasonic equipment, radiation therapy, MRI, theft detectors/ screening devices. Adverse events include pain at the implant sites, new pain, lead migration, infection, technical or device problems, adverse change in bowel or voiding function, and undesirable stimulation or sensations, including jolting or shock sensations. For full prescribing information, please call Medtronic at 1-800-328-0810 and/or consult Medtronic’s website at www.medtronic.com. Product technical manual must be reviewed prior to use for detailed disclosure. USA Rx Only. Rev 0409

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