Home

User Manual - MarginProbe

1. PB0501071 5 2 MARGINPROBE User Manual Operating Instructions Connect the Probe outside the Sterile Field The length of the probe cable is 2 7 meters 8 feet 10 inches to enable proper maintenance of the sterile field around the patient 1 2 Circulating Nurse open the probe s box and remove the plastic blister from the box Circulating Nurse open the plastic blister outside the sterile field Scrub Nurse remove the sterile probe from the blister and hand the connector out of the sterile field Circulating Nurse insert the probe connector into the system s connection port Turn the connector one half turn to the right clockwise until you feel it reaches its position Figure 5 3 vA Note Note The connector and the port are both notched to prevent incorrect insertion Caution AN e Although the console s connector is covered visually check it to ensure that there are no foreign objects in the connector every time before connecting a new probe e Do not use a new probe if the package is damaged If the package was dropped visually inspect the probe and do not use if damaged Figure 5 3 Probe Connection Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 3 MARGINPROBE User Manual Operating Instructions Operating the System The system senses that a probe has been connected and automatically proceeds to the calibration process
2. Please Contact Service The system has detected a fatal internal error Contact Dune Medical Service Measurement initialization failure Replace Probe The system detected an error in the probe calibration or measurement process Replace the probe and contact Dune Medical Service Probe failure Replace Probe The probe data was corrupted Replace the probe and contact Dune Medical Service Unrecognized Probe was connected A general problem was found in the probe Replace the probe and contact Dune Medical Service Probe has expired The probe expiration date has passed Replace the probe limit 1 Probe has reached time The probe has reached its usage limit Probe can no longer be used for reliable measurements Replace the probe limit 2 Probe has reached time The probe has reached its usage limit Probe can no longer be used for reliable measurements Replace the probe limit 3 Probe has reached time The probe has reached its usage limit Probe can no longer be used for reliable measurements Replace the probe capacity limit Probe has reached its The probe has reached its usage limit Probe can no longer be used for reliable measurements Replace the probe this Console Probe is not valid with Probe was connected to a different Console in the past Replace the probe Caution Federal law restricts this de
3. 100 0 initiated Effectiveness Sets AVS All Randomized Patients 298 298 NA 596 100 0 100 0 100 0 PSS Positive Specimen Patients 163 147 NA 310 54 7 49 3 52 0 NSS Negative Specimen Patients 135 151 NA 286 45 3 50 7 48 0 All randomized patients completed the study protocol There was no loss to follow up in the study There was no missing data related to the CSR endpoint 38 1788 2 of margins were not measured by the device C Demographics and Baseline Characteristics Demographic characteristics were similar for the Device and Control groups Overall the groups appeared to be comparable as shown in Table 2 8 and 2 9 Table 2 8 Demographics by Treatment Group Treatment Group Roll In Device Control Parameter N 68 N 298 N 298 Ethnic Origin n White 59 86 8 250 83 9 260 87 2 African American or Black 5 7 4 22 7 4 17 5 7 Asian 2 2 9 12 4 0 10 3 4 Native Hawaiian or Other 0 0 3 1 0 1 0 3 Pacific Islander Other 2 2 9 11 3 7 10 3 4 Includes Hispanics Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 13 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 9 Baseline Characteristics by Treatment Group Treatment Group Roll In Device Control Parameter N 68 N 298 N 298 Age yrs Mean
4. 0 0 0 0 0 0 1 1 0 a APNEA Infections abscess o 1 1 0 0 0 1 1 0 ane Cellulitis 0 0 0 0 0 1 wound infection 1 ro lo 00 oc 1 1 0 e lo aja alioli lio infection om lo o l 1M 1 10 Aay a AAA 31 O 00 Fractured m aAa Injury Post a Ed e and haemorrhage 0 0 2 2 1 0 0 2 2 0 p rocedural Procedural oe hos es 1 jo 00 ied 0 0 0 0 1 1 0 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 18 MARGINPROBE User Manual Safety amp Regulatory Issues Control Roll In Phase System Organ TENG N 298 N 68 Class Preferred N N N Term eae EN aoe SAEs Patients SAEs Patients SAEs Reproductive system and breast disorders Vascular disorders Treatment Group 0 0 1 1 0 o Breast haematoma 0 0 EN o0 1 1 0 o 1 0 mM 0 0 ied 1 An i o ow 1 10 o 00 10 EOT Hypertensive crisis 1 0 0 0 0 0 1 1 0 Adverse events associated with device malfunction or incorrect device readings causing incorrect surgeon action is both a safety and an effectiveness issue Incorrect surgeon action is therefore further discussed in the Effectiveness Results section below While an approximately 5 minute prolongation of the operative procedure associated with device use this prolongation cannot be associated with specific patient adverse events In addition while damage
5. Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 Page 1 1 MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Safety amp Regulatory Issues 2 SAFETY AND REGULATORY ISSUES This chapter describes the safety issues regarding the use and maintenance of the MARGINPROBE system with special emphasis on electrical safety The system is designed for safe and reliable use when used in accordance with proper operation procedures The user and all other personnel operating the system should be familiar with the safety information provided in this chapter Dune Medical assumes no liability whatsoever for any damage or injury as a result of an application of a product which is not in strict accordance with the instructions provided with the product Warning e Read this chapter to be familiar with all of its safety requirements and operating procedures prior to operating the system e The MARGINPROBE probe is designed for use only with the MARGINPROBE console e High voltage is present inside the console e Always be aware of the possible dangers and take proper safeguards as described in this guide e For complete contact information please refer to page A of this manual Intended Use The Dune MARGINPROBE System is an adjun
6. MARGINPROBE User Manual Operating Instructions System Shut Down To shut down the MARGINPROBE system Press the start shutdown switch on the control panel for three seconds the system will start the shutdown process and a pop up message will appear stating System preparing to shutdown Press Power button to cancel Figure 5 11 After several seconds the system will power down and the power LED will turn orange In order to cancel the shutdown process press the start shutdown switch again Pressing the start shutdown switch for less than three seconds will not initiate the shutdown process Turn off the main power switch on the lower rear panel after shutdown process is complete System preparing for shutdown Press power button to cancel Figure 5 11 Shutdown Message Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 13 MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Maintenance 6 MAINTENANCE Introduction The MARGINPROBE system is designed to operate reliably without any need for operator maintenance However the outer surfaces of the system should be kept clean and free of dust Warning System cleaning should be performed only when the system is shut down and disconnected from the main power sour
7. PBO0501071 3 4 MARGINPROBE User Manual System Description 4 SYSTEM DESCRIPTION Introduction The MARGINPROBE system consists of a console and a sterile disposable probe The MARGINPROBE console consists of internal electrical components a pneumatic system and a graphic user interface module The user interface module incorporates a color display audio components and operation buttons Figure 4 1 MARGINPROBE System Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 4 1 MARGINPROBE User Manual System Description Console The console Figure 4 2 incorporates modules for signal generation and collection electric and pneumatic control data processing and display The console includes a connector for attaching the probe cable LCD Screen Control Panel Handle gt gt Main Console including Module for signal generation and collection electric amp pneumatic control On Rear Panel Data processing amp display Main rones v4 ain Power Switc Isolation Transformer Wheel Brake Pedal On Bottom Panel Heat Dissipation Fans Figure 4 2 System Description Console Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 4 2 MARGINPROBE User Manual System Description Control Panel The control panel on the front of the console incorporates all system controls as noted in Fig
8. SD 63 6 11 1 60 3 11 4 60 2 11 1 BMI mean 28 0 27 9 28 6 Bra Cup Size n AA 0 0 0 2 0 7 4 1 3 A 6 8 8 16 5 4 16 5 4 B 21 30 9 101 33 9 73 24 5 C 24 35 3 99 33 2 93 31 2 D 12 17 6 62 20 8 92 30 9 E 1 1 5 2 0 7 5 1 7 F 1 1 5 1 0 3 1 0 3 gt F 1 1 5 1 0 3 2 0 7 Unknown 2 2 9 14 4 7 12 4 0 Table 2 10 presents the number of patients with a diagnosis requiring that certain categories be combined For patients with invasive types of carcinoma the mixed invasive category was used and for patients with more than diagnosis who did not have more than one type of invasive carcinoma the mixed category was used The treatment groups appear to be similar with respect to diagnosis Table 2 10 Patient Diagnosis by Treatment Group Per diagnosis Analysis Patient Diagnosis Treatment Group Device Control Roll In Phase All N Patients N Patients N Patients N Invasive Ductal Carcinoma 24 8 1 22 7 4 7 10 3 53 8 0 Invasive Lobular Carcinoma 26 8 7 13 4 4 2 2 9 41 6 2 Mixed Invasive 8 2 7 5 1 7 1 1 5 14 2 1 Ductal Carcinoma in Situ 83 27 9 78 26 2 19 27 9 180 27 1 Tubular Carcinoma 1 0 3 0 0 0 0 0 0 1 0 2 IMucinous Carcinoma 1 0 3 1 0 3 0 0 0 2 0 3 Mixed 155 52 0 179 60 1 39 57 4 373 56 2 Total 298 100 0 298 100 0 68 100 0 664 100 0 a Mixed inv
9. as the initial lumpectomy can reduce the incidence of incomplete cancer resection and produces greater volumes of tissue resection Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 30 MARGINPROBE User Manual Study V Sites 1 amp 2 Selective Shaving Main Specimen Margin Status 68 Shavings Shavings Not taken 44 taken 22 Histo Histo Histo Margin on Margin on Margin on Final Final Final Pathology Pathology Pathology 35 9 22 Safety amp Regulatory Issues Volume excised SOC 110 Site 1 52 cc 95 Cl 44 60 Site 2 89 cc 95 Cl 63 115 Main Specimen Margin Status 42 Shavings Shavings Not taken 27 taken 15 Histo Histo Histo Margin on Margin Margin on Final on Final Final Pathology Pathology Pathology 0 27 15 Main Specimen TR gt o o Final Margin OOO _ T SS Totals 9 68 57 68 0 42 42 42 Figure 2 9 Study V Final Pathologies from Patients Treated at Study Sites 1 and 2 Selective Re excision Study V Site 3 Routing Shaving Main Specimen Margin Status 31 Shavings Shavings Not taken 30 taken 1 Histo Histo Histo Margin on Margin on Margin on Final Final Final Pathology Pathology Pathology 2 2 8 1 SOC 66 Volume excised Site 3 113 cc 95 Cl 100 26 oe Main Specimen Margin Status 35 Shavings Shavings Not taken 32 taken 3 Histo Histo Histo Margin o
10. specimen detected by device Rate of repeated ipsilateral breast surgical procedures including mastectomies Positive Margin Presence Rate of patients with at least 1 positive margin remaining after lumpectomy TTV excised in the primary lumpectomy procedure cm Average volume of total amount of tissue excised in lumpectomy 6 Pre Specified Analysis Plan For the primary efficacy analysis a sample size of 116 valid primary effectiveness patients per arm was determined to provide at least 90 power to demonstrate superiority of SOC Device over SOC The analysis populations are defined in Table 2 3 Table 2 3 Analysis Populations putes Definition Population All Valid Subjects The AVS subjects included all randomized patients with valid AVS histology data and valid MarginProbe System data in Device arm Positive Specimen The PSS subject is a subset of the AVS Analysis Set of subjects Subjects PSS with at least 1 histologically positive main specimen margin at depth lt 1 mm Negative Specimen The NSS subject is a subset of the AVS Analysis Set of subjects Subjects NSS with no histologically positive main specimen margin at depth lt 1 mm Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 10 MARGINPROBE User Manual Safety amp Regulatory Issues Safety was assessed using the AVS population The primar
11. unless resected in a single specimen Bilateral disease diagnosed cancer in both breasts Neoadjuvant systemic therapy Previous radiation in the operated breast Prior surgery at the same site in breast Implants in the operated breast Pregnancy Lactation Cryo assisted localization Precautions The main ex vivo lumpectomy specimen is defined as the initially excised lumpectomy specimen without any of the lumpectomy cavity shavings that may have been subsequently taken during the procedure The device has not been studied for use on tissue shavings excised from the lumpectomy cavity The MARGINPROBE system should be used in addition to standard intraoperative methods of assessing margin status Moving the probe before suction release may potentially damage and affect tissue histopathology The MARGINPROBE Probe should only be used with the MARGINPROBE Console The MARGINPROBE Probe is designed for single patient single use only and must be properly discarded after use The MARGINPROBE Probe is supplied sterile If the sterile pack is torn or has been opened do not use the probe Do not use a MARGINPROBE Probe that has passed its expiration date Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 2 MARGINPROBE User Manual Safety amp Regulatory Issues Potential Adverse Effects of the Device on Health Below is a list of the potential adverse
12. 12 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Table of Content Clearing the Screen and Removing Popup Messages cccococcccccnocccccononcccnononnnccnnnnncncnanancncnnannnnnnnns 5 12 Stand by Mode ud lada al A EEA RE db 5 12 System Shur DON vta rt DEA A ada ad 5 13 6 Maintenance Arere A E AA A da a 6 1 IntroductiOn ii a es E al ere r ree 6 1 Exterior Cleaning iio tidad beat 6 1 Interior INSPSCUOM A nsii testi iii italia 6 1 SEMVICS Information 225 ccxkacdiieiendericecaanteiacdatecedds tached aenceesti del coke EO ehesdescett qa 6 1 STOMA aes ee eu eee ee de edie ees 6 2 Te Troubleshooting A ie Adee ties eee A 7 1 INTO CON A ance de ee ea ee 7 1 Troubleshooting GUIAES ccoo cd A ca edo 7 1 ASE Se a AA ee dete die ee 8 1 System PSMONMNANGCE caian aia 8 1 Environmental Requirement oooocccocococcccccnccoconononnnnnnnncnnnnnn no nnnn cnn nn nn nn nn nn rn nn nn enn nn nn nnnnnrnnnnnnnnnnnnrnniniannmes 8 1 Physical SpeCiiCations iii Oia 8 1 Electrical Specifications a a A a eee a a A Sa Daaa aa Aa Aa AAAA ae AA Ee iaei aaa i EEEa 8 1 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Table of Content LIST OF FIGURES Elgure 2 1 Prota study Desi ti dit odias 2 5 Figure 2 2 Illustration of CSR Primary Endpoint ooccccccconnccoccnnnnconcnnoncnncnn on n o nan
13. 6 margins was suture marked Patient were then randomized to either the SOC or SOC Device arm intraoperatively immediately after the main lumpectomy specimen was excised oriented center marked palpated and additional palpation based re excision performed For patients randomized to the SOC Device arm the surgeon e Applied the MarginProbe device to each of the 6 faces of the excised main lumpectomy specimen sampling 5 8 points and up to 12 points for larger specimens The points sampled were at both evenly spaced and suspicious sites e Was required to react to Device feedback A single positive reading on any margin classified that margin as positive and required the surgeon to remove additional tissue from that margin e Documented the reasons why additional margins were not re exicised despite a positive MarginProbe device reading For the purposes of CSR primary endpoint Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 4 MARGINPROBE User Manual Safety amp Regulatory Issues calculations lumpectomy cavity shavings that were not possible due to physical limitations proximity to the skin or pectoralis fascia the margin was considered addressed e Was instructed not to use the MarginProbe device on shavings from the lumpectomy cavity shavings even if a shaving was taken prior to randomization e Was instructed not to use the MarginProbe device within the in viv
14. 7 Device SOC 27 6 19 6 36 0 44 7 54 0 34 9 8 2 13 5 3 7 6 16 6 27 9 t PPV and NPV calculated using Bayes theorem assuming a common prevalence across the two study arms of 52 195 Bootstrap percentile intervals Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 21 MARGINPROBE User Manual Safety amp Regulatory Issues The Figures 2 3 and 2 4 provide a more comprehensive assessment of what occurred in each arm of pivotal study As shown in Figure 2 4 298 SOC patients were enrolled An average of 72 cm3 of tissue was excised during the initial lumpectomy There were 147 patients with cancer positive main specimens and 151 cancer negative main specimens Of the 147 cancer positive main specimens 25 or 17 were converted to cancer negative final margins with cavity shavings In the SOC arm shavings were not taken in 46 81 or 127 298 subjects Volume excised 72 cm 95 Cl 65 25 78 66 Pivotal Study SOC l SOC 298 Average Main Specimen Main Specimen shavings Margin Status Average Margin ar 1 30 147 shavings 0 91 Shavings Shavings Not Shavings Shavings Not taken 101 taken 46 taken 70 taken 81 Histo Histo Histo Histo Histo Histo Margin on Margin on Margin on Margin on Margin Margin on Final Final Final Final on Final Final Pathology Pathology Pathology Pathology Pathology Pathology 76 25 46 2 68 81 Main Specimen Final
15. Figure 2 7 This figure includes three datasets 1 tissues containing at least 75 of a single tissue type 2 all tissues containing at least 50 of a single tissue type and 3 the full dataset collected in the experiment containing cancers of all sizes down to 0 15 mm diameter features Sensitivity amp gt 50 of one tissue type Full dataset Ue 1 0 20 40 60 80 100 FP rate 100 specificity Figure 2 7 Study HI ROC curves of 3 different datasets When the composition of the tissue being measured by the probe i e directly underneath the 7 mm footprint of the probe was more homogeneous there was greater sensitivity and specificity in MarginProbe readings as shown in Table 2 28 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 28 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 28 Study III Sensitivity and Specificity in MarginProbe Readings Percentage single tissue type within probe s 7 mm diameter footprint Specimen description Device Performance gt 75 singe tissue type 22 cancerous from 15 patients 425 nonmalignant Sensitivity 1 00 95 CI 0 85 1 Specificity 0 87 95 CI 0 83 0 90 gt 50 single tissue type 29 cancerous from 18 patients and 567 nonmalignant Sensitivity 1 00 95 CI 0 88 1 Specificity 0 72 95 CI 0 68 0 76 Full dataset c
16. MARGINPROBE O NO 4 1 Figure 4 2 System Description CONSOl8 oooooonnnoccnnnnncocannnononcnnnonancnonono nana r anno naar anno nc r rn rar rra 4 2 Figure 4 3 System Description Control Panel ooccnnnocccnnnnocinnnococnnononancnn nono nc nr nano cnn rro narran rra 4 3 Figure 4 4 Graphic User Interface onooccinnnccccnnnococcnnnonaccnnnnnnn cnn nono cnn nn cnn non 4 4 Figure 4 5 System Description Probe onnccccnnnncccnonnocccnnnnononannnnno nano nnno nana r nn nara nn arras 4 5 Figure 4 6 Probe lip ia a IA ata 4 6 Figure 4 7 Control Button and Probe LEDS oonnccccinncocconnoccncnnnonnnncnonononcnnnnn ona nr ERREKAK KANARA ERR ERANT ERREKAR KAERA 4 6 Figure 4 8 Probe Conectada 4 7 Figure 5 1 Connect Probe Popup WiNdOW ccccceecseccececeeeeeeecaeeeeeeeeeeeesceaeaeeeeeeeseseccaeaeeeeeeeseeeeninaees 5 2 Figure 5 2 Standby Mode Message ooocooonococonnnoccccnonononcnnnononnnnnnnnnnn Er E RETE anne rra NENA 5 2 Higie S o Probe COMECtON ici ld dida 5 3 Figure 5 4 Calibrating Message oooonnnccccnnncococnnioccccnnnnnoncnnonnn cnn anian Kiia erada EASTA KAEA rare rra 5 4 Figure 5 5 New Probe Screen enisinia dd dd dd da 5 5 Figure 5 6 choosing the Margin to be measured c nnncccccnnocociconononcnnnononannnnnnoncnnnnnn nc nrnnnn nn arrnnn rra rr nnn rca 5 6 Figure 5 7 Confirmed Chosen MargiN oooonncccinnnnnoccnnnocccnnn nono ncnnnnono nc anno cnn nro rn rana 5 7 Figure 5 8 Probe Tip Application to the SpeciMen ooooco
17. Margin 9 0 o Totals 17 25 147 83 122 147 1 3 2 151 98 7 149 151 Figure 2 4 Pivotal Study Patient Flow Chart SOC Arm As demonstrated in Figure 2 5 298 patients were enrolled in the SOC Device arm An average of 88 cm3 of tissue was excised during the initial lumpectomy There were 163 patients with cancer positive main specimens and 135 cancer negative main specimens Ofthe 163 cancer positive main specimens 79 or 49 were converted to cancer negative final margins with cavity shavings In the SOC Device arm shavings were not taken in 2 8 or 10 298 subjects Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 22 MARGINPROBE User Manual Pivotal Study SOC Device Average Main Specimen shavings Margin Status 3 57 163 SOC Device 298 Average shavings 2 88 r Safety amp Regulatory Issues Volume excised 88 cm 95 CI 78 91 96 13 Main Specimen Margin Status 135 n Shavings Shavings Not Shavings Shavings Not taken 161 taken 2 taken 127 taken 8 Histo Histo Histo Histo Histo Histo Margin on Margin on Margin on Margin on Margin Margin on Final Final Final Final on Final Final Pathology Pathology Pathology Pathology Pathology Pathology 82 79 2 8 119 8 Main Specimen Final Margin Totals 48 5 79 163 51 5 84 163 5 9 8 135 94 1 127 135 Figure 2 5 Pivotal S
18. effects e g complications associated with the use of the device e Extension of procedure time e Errors in device reading e Unnecessary removal of healthy tissue with a potential negative impact on cosmetic results or cosmetic appearance e Infection e Local tissue damage e Bleeding For the specific adverse events that occurred in the clinical studies please see the next section Clinical Data below Clinical Data MarginProbe Pivotal Study Dune Medical Inc performed a clinical pivotal study to establish a reasonable assurance of safety and effectiveness of the MarginProbe System The MarginProbe System is an adjunctive diagnostic tool for identification of cancerous tissue at the margins lt 1mm of the ex vivo lumpectomy specimen following primary excision and is indicated for intraoperative use in conjunction with standard methods such as intraoperative imaging and palpation in patients undergoing breast lumpectomy surgery for previously diagnosed breast cancer in the US The pivotal study was performed under IDE G070182 Data from this clinical study were the basis for the PMA approval decision A summary of the clinical study is presented below A Study Design Patients were treated between September 2008 and March 2010 The MarginProbe System pivotal study was a prospective multicenter randomized 1 1 controlled double arm study Breast cancer patients were randomized to either receive standard of care SO
19. measurement E es Disconnect and reconnect the probe after connecting the connection If problem persists restart the system probe Probe If problem persists after restarting the Connect Probe malfunction system replace the probe message persists Svst If problem persists after replacing the after probe A probe contact Dune Medical connection malfunction No sound is heard upon completion of measurement Press volume up button on control panel pressing the volume up down Noise lsckorsouna button should produce an audible does not indicate e System is pies l l system malfunction muted Continue normal operation using and the system may e System screen and LED indications be used without the speaker Restart system at the end of the audible indication malfunction procedure and check the sound by Screen and LED indications are accurate even in the absence of the audible indication pressing the up down volume button If problem persists contact Dune Medical Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 7 4 MARGINPROBE User Manual System Specification 8 SYSTEM SPECIFICATIONS System Performance e Effective measurement area e Detection depth e Tissue type e System warm up time e Measurement time from tissue attachment to results display 7 0 mm lt 1 mm Detection of in situ and invasive ductal and lobular bre
20. that turns green when exposed to ethylene oxide and indicates that the contents of the pack are sterile If the indicator on the probe s sealed pack is any other color than green or if the indicator is missing do not use the probe Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 35 MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Console Placement 3 CONSOLE PLACEMENT Equipment List The MARGINPROBE console shipment package contains the following Equipment Item Quantity MARGINPROBE Console 1 USER Manual English this document 1 Facility Requirements Before unpacking the system ensure that the site meets the requirements described in the following sections Electrical Requirements The system will require a separate line supply for the following appropriate to local requirements 230VAC 50Hz or 115VAC 60Hz single phase The electrical requirements are printed on the console identification label located on the console s rear panel Warning To ensure safe operation the system must be connected to a properly grounded electrical wall socket Space Requirements Space should be allocated with adequate ventilation and free airflow The working area for the system should be pr
21. to either the roll in group or randomization enrollment allocation Sixty eight women were operated on in the roll in phase and 596 were randomized equally to the Control SOC arm and Device treatment Device SOC arm groups All 664 women completed the study Subject accountability is displayed below in Table 2 6 Table 2 6 Patient Accountability Pivotal Study Disposition Total n Eligible for Participation 721 Did Not Enter Study 57 7 9 Failed eligibility 25 3 5 Withdrew consent 6 0 8 Other 26 3 5 Eligible for Allocation 664 92 1 Allocated to Enrollment 664 100 Roll in 68 10 2 Randomized to Treatment 596 89 8 Device 298 44 9 Control 298 44 9 Completed Study 664 100 Did Not Complete 0 0 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 12 MARGINPROBE User Manual Safety amp Regulatory Issues All 664 women were included in the Safety analysis set The AVS analysis set includes 596 randomized 298 Device and 298 Control patients and differs from safety analysis set in 64 roll in women as shown in Table 2 7 Table 2 7 Data Sets Analyzed Number of Patients Treatment Group Device Control Roll In Total Analysis Set Patients Included n n n n Safety Set All patients for whom 298 298 68 664 surgical procedure was 100 0 100 0 100 0
22. to the tissue exposed to the MarginProbe device is a potential problem an assessment for tissue damage was not considered to be feasible in the pivotal study From the available data this issue has not been reported 2 Effectiveness Results Primary Effectiveness Endpoint There were a total of 163 patients in the SOC Device arm and a total of 147 patients in the SOC arm who were in the PSS dataset 1 e with at least one positive margin by histology on the main specimen The CSR primary effectiveness endpoint results are provided in Table 2 19 The device failed to give a reading on 38 2 margins out of 1788 margins measured from 298 subjects This did not impact the primary endpoint Table 2 19 The CSR Primary Effectiveness Endpoint Results Primary SOC Difference Endpoint Dataset Denis SOC 95 CD 71 8 22 4 49 3 p lt 117 163 33 147 39 0 58 7 0 0001 CSR PSS Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 19 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 20 Secondary Effectiveness Endpoint Results Secondary Dataset SOC SOC p value or CI Endpoints Device Incomplete 15 4 38 3 p lt 0 0001 Surgical 46 298 114 298 Re excision Full Detection 62 6 NA 95 CI 102 163 54 7 70 Re excision 20 8 25 8 p 0 3177 Procedure Rate 82 298 94 298 Positive Margin 30 9 41 6 p 0 0082 Presen
23. visualization palpation positive MarginProbe device readings imaging touch prep cytology or frozen section analysis was not documented The methods of excision used during lumpectomy included the following electrocautery sharp excision and scissors Table 2 14 describes number of patients undergoing SLNB with dye or radioisotope or both Table 2 14 Number of Patients undergoing SLNB with Dye or Radioisotope or Both Roll In Device Control N 68 N 298 N 298 SLNB performed 59 72 223 75 225 75 E Pathology Table 2 15 presents weight and volume of the main specimen There were no apparent differences between treatment groups with respect to weight and volume of the main specimen The mean size diameter of the main specimen was 4 85 cm for the Device group 4 89 cm for the Control group and 4 7 cm for the Roll in group Table 2 15 Descriptive Statistics of Specimen Weight and Volume by Treatment Group Specimen Device Control Roll InPhase Parameter m Mean SD n Mean SD n Mean SD m Mean SD Weight g 294 51 4 42 2 290 55 8 49 8 Volume cm 296 59 7 51 4 298 61 3 52 5 68 54 6 67 5 662 59 9 53 7 Source Statistical Table M 46 in Appendix 10 2 2 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 16 MARGINPROBE User Manual Safety amp Regulatory Issues Overall mean tumor size
24. was not documented Questionable clinical relevance CSR considers whether a shaving was taken or not taken at positive margins on a lumpectomy specimen CSR does not consider whether the shaving taken converted the initially positive for cancer margin to a negative for cancer final margin CSR does not penalize false positive MarginProbe readings in the positive main specimen cohort False positive MarginProbe readings in the positive main specimen cohort cause the resection of healthy tissue CSR does not consider false positive MarginProbe readings in the negative main specimen cohort False positive MarginProbe readings in the negative main specimen cohort cause the resection of healthy tissue Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 9 MARGINPROBE User Manual Safety amp Regulatory Issues Secondary effectiveness endpoints are summarized in Table 2 2 below Table 2 2 Secondary Effectiveness Endpoints Endpoint Definition Incomplete Surgical Re excision Proportion of patients with at least 1 positive margin not resected addressed Differs from primary effectiveness endpoint CSR since Yes No definitions are opposite Differs from the CSR endpoint since it is calculated from the AVS dataset rather than the PSS dataset Full Detection Re excision Procedure Rate Rate of patients with all positive margins on main
25. was similar for the groups MarginProbe 1 7 cm Control 1 6 cm The tumor type as assessed by post operative histopathology by treatment group are presented in Table 2 16 The treatment groups appear to be similar with respect to tumor type The number of positive margins on the main specimen by treatment group also appears to be similar Table 2 16 Frequency Distribution for Tumor Type by Treatment Group Treatment Group Tumor Type Device Control Roll In Phase de N Specimens N Specimens N Specimens N Specimens Invasive ductal 158 53 0 179 60 1 40 58 8 377 56 8 ple 46 15 4 26 8 7 9 13 2 81 12 2 Ductal carcinoma in situ 207 69 5 229 76 8 46 67 6 482 72 6 Tubular Carcinoma 5 1 7 6 2 0 2 2 9 13 2 0 Mucinous Carcinoma 10 3 4 3 1 0 2 2 9 15 2 3 Medullary Carcinoma 0 0 0 0 0 0 0 0 0 0 0 0 Papillary Carcinoma 0 0 0 2 0 7 1 1 5 3 0 5 Non malignant NM 19 6 4 19 6 4 5 7 4 43 6 5 Other 5 1 7 7 2 3 0 0 0 12 1 8 Total Patients 298 100 0 298 100 0 68 100 0 664 100 0 The average weight and volume of resected margins by treatment group during the lumpectomy is presented in Table 2 17 The treatment groups appear to be similar with respect to weight and volume of resected margins Table 2 17 Descriptive Statistics of Resected Margins Weight and Volume by Treatment Group Devic
26. C lumpectomy or Standard of Care lumpectomy with adjunctive MarginProbe device use SOC Device Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 3 MARGINPROBE User Manual Safety amp Regulatory Issues Key Aspects of the protocol are as follows 1 Patient Study Inclusion and Exclusion Criteria Enrollment in the pivotal study was limited to patients who met the following inclusion criteria e Women histologically diagnosed with carcinoma of the breast e Women with non palpable malignant lesions requiring image guided localization e Undergoing lumpectomy partial mastectomy procedure e Age 18 years or more e Signed informed consent form Patients were not permitted to enroll in the pivotal study if they met any of the following exclusion criteria e Miulticentric disease histologically diagnosed cancer in two different quadrants of the breast Bilateral disease diagnosed cancer in both breasts Neoadjuvant systemic therapy Previous radiation in the operated breast Prior surgical procedure in the same breast Implants in the operated breast Pregnancy Lactation 2 Patient Treatment Patients were first enrolled and taken to the operating room for resection of the main lumpectomy specimen The main lumpectomy specimen and lumpectomy cavity palpation and related re excisions were performed before patient randomization For all main specimens the center of each of the
27. DUNE Medical Devices MARGINPROBE User Manual User Manual P N PB0501071 Caution Federal law restricts this device to sale by or on the order of a physician MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual COPYRIGHT 2012 Dune Medical Devices Ltd All rights reserved worldwide This work and all rights herein are owned exclusively by Dune Medical Devices Ltd its subsidiaries and its other affiliated corporations No parts of this manual in whole or in part may be reproduced performed published displayed broadcast translated or transmitted to any electronic medium or machine readable form distributed sold or otherwise used or relied upon without the express prior written permission of Dune Medical Devices Ltd Reproduction or reverse engineering of copyrighted software is prohibited PATENTS This product is protected by the following US Patents 7 899 515 7 904 145 8 019 411 8 147 423 8 195 282 8 319 502 This product is protected by the following Chinese Patent ZL200680019026 4 Other patent applications are pending in the USA China Japan and Europe including EP1890596 EP1919273 EP2118801 EP2129281 EP2304456 TRADEMARKS A Medical Devices A is a registered trademark of Dune Medical Devices Ltd e DUNE is a registered trademark of Dune Medical Device
28. EDs Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 4 6 MARGINPROBE User Manual System Description Probe LEDs The probe features three LEDs Figure 4 5 and Figure 4 7 each one signifying a different result of a point measurement during calibration and in standby mode all the LEDs will be turned on Refer to the Operating Instructions chapter for complete details section 5 Probe Connector The probe connector Figure 4 8 and Figure 5 3 couples the probe to the MARGINPROBE console The body of the connector and the connection port are notched to each other with a dimple on the inner rim of the connector and a depression for the dimple in the rim of the port so that the connector may only be inserted in the correct orientation A half turn to the right locks the connector in place Figure 4 8 Probe Connector Caution Federal law restricts this device to sale by or on the order of a physician PBO0501071 4 7 MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Operating Instructions 5 OPERATING INSTRUCTIONS Introduction The probe was designed to measure breast tissue Before performing a measurement on the specimen make sure that the specimen is wiped free of excess fluid Do not apply saline or ultraso
29. Federal law restricts this device to sale by or on the order of a physician PB0501071 2 33 MARGINPROBE User Manual Safety amp Regulatory Issues Electrical and Mechanical Safety Precautions There are no user serviceable parts inside the system Make sure that all personnel are familiar with the system s controls and know how to shut down the system instantly in case of an emergency Keep all covers and panels of the system closed Removing the covers creates a safety hazard Any handling of the system other than intraoperative use should be performed when the system is shut down and disconnected from its electrical power source Move the system slowly and carefully The system weighs approximately 82 kg 180 lbs and may cause injury if proper care is not used The system is grounded through the grounding conductor in the power cable This protective grounding is essential for safe operation Portable and mobile communications equipment and OR electrical equipment can affect medical electrical devices Interference may occur in the vicinity of the equipment Do not use any accessories or cables other than those specified and provided Use of such accessories or cables may result in damage to the system Connecting any third party equipment to the system is strictly forbidden without written approval from Dune Medical Compliance with International Regulatory Standards The MARGINPROBE system complies with the requireme
30. asive Invasive Ductal Carcinoma Invasive Lobular Carcinoma b Mixed more than 1 diagnosis and not only invasive carcinoma Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 14 MARGINPROBE User Manual Safety amp Regulatory Issues Tumor stage results are presented in Table 2 11 below The majority of patients were diagnosed with stage II breast cancer and below Table 2 11 Tumor Stage 0 I II Ill IV Unknown Total Treatment N T N A NIAI NIM NIAI NIA NT Group Device 81 127 2 155152 0 51 117 1 13 1 10 31 6 2 0 298 100 0 Control 84 28 2 161 54 0 44 14 8 2 0 0 0 3 1 0 298 100 0 Roll In 21 30 9 34 50 0 12 17 6 1 15 0 0 0 0 68 100 0 Phase All 186 28 01 350 152 7 107 16 1 11 1 7 1 10 21 9 1 4 664 100 0 Receptor status is presented in Table 2 12 There were 84 subjects in device and control arms and 19 in the roll in subjects for which HER2 status was not preformed Table 2 12 Receptor Status Receptor Status Ree on ay ER 60 68 88 2 251 84 2 258 86 6 PR 52 68 76 4 223 74 8 217 72 8 HER2 3 49 6 20 214 9 33 214 15 HER2 42 49 85 175 214 82 163 214 76 D Surgical Procedure The mean duration of anesthesia time hours minutes was 2 03 for the Device group 1 52 for the Control group and 2 11 for the Ro
31. ast carcinoma lt 3 minutes about 3 seconds Environmental Requirements e Room temperature e Relative humidity Physical Specifications e Console dimensions WxDxH e Console weight e Probe dimensions LxW e Probe box dimensions WxDxH Electrical Specifications e AC Power requirements e Max AC power e Max output to probe 15 C to 30 C 59 F to 86 F 30 to 80 at temperature lt 29 C 84 F 60 x 60 x 145 cm 23 6 x 23 6 x 57 inches lt 85 Kg 187 Lbs 197 x 23 mm 7 8 x 0 9 inches 34x25x5cm 13 4 x 9 9 x 2 inches 230VAC 50Hz or 115VAC 60Hz single phase 200 VA 1 dbm 1mW Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 8 1 MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071
32. be can easily be removed from the tissue The table below summarizes possible system outputs Table 5 1 Possible System Measurement Outputs Figure 5 9 IT LED Color System Tone Screen Reaction Indication Positive malignant tissue Single Beep Red bar above i detected Red line RED Negative no v malignant tissue gt pu Double Beep Blue bar below detected Blue line BLUE Failed Measurement Yellow Error Tone Empty Bar Lift the probe after each system tone sounds If the probe is left on the tissue after the tone an additional measurement will be taken automatically A Caution e Lift the probe only after the tone sounds in order to prevent tearing of the tissue e Attach the probe tip only to tissue and avoid direct contact with other materials or surgical tools Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Operating Instructions Attempt to evenly sample each margin surface area In addition suspect areas may be sampled as deemed necessary In case of failed measurements indicated by a blank bar repeat the measurement As mentioned above the probe is designed for single use can only be connected to one console and can obtain a limited number of measurements There is a time limitation for using the probe once it has been connected to the console When 30 or fewer measurements remai
33. be paired with their histology at point level For each point measured with the device the pathology was taken at that same point Device measurements were performed at the interior of the lumpectomy specimen following its sectioning at the pathology lab The specimens used for this study were taken from women with palpable tumors who had undergone lumpectomy or mastectomy The study was performed in Israel at 4 study sites The patient demographics and cancer specifics of the specimens used to create the classification dataset are summarized in Table 2 26 Table 2 27 illustrates the classification data set that was derived in Study III Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 26 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 26 Study III Patient Demographics and Cancer Specifics 77 patients and 81 specimens 4 patients bilateral disease Mean Age range 62 64 years 36 85 Mean Tumor Size range 1 65 cm 0 1 3 5 Sentinel Node Biopsy 43 specimens Both Blue Dye amp Radioisotope Cancer Pathology aero Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 27 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 27 Study III Classification Data Set INumber of tissue measurement data points The ROC curves of the device performance in Study III are shown in
34. bration module control button LED indicators and biological air filter It is connected to the console with a built in connector that combines electrical and vacuum connections The energy is electromagnetic at the RF range It is confined to the vicinity of the probe tip The energy level per measurement is less than 0 2 mJ with a power lower than 0 3 mW The max field voltage is 1V p p Probe Connector Air Filter Control Button Y Probe Assembly 3 LED Indicators Figure 4 5 System Description Probe Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 4 5 MARGINPROBE User Manual System Description Coupling and Measurement The tip of the probe incorporates the tissue sensor attachment mechanism and the sensor that measures the tissue Attachment Sensor Plate Mechanism Figure 4 6 Probe Tip Probe Control Button The system can be operated during a procedure by pressing the control button Figure 4 7 e Double Click for opening and closing measurement frames refer to Operating Instructions section 5 p 5 6 e Single Click for designating the measurement frames refer to Operating Instructions section 5 p 5 6 e Long Click for editing and confirming groups of measurement points refer to Operating Instructions section 5 p 5 7 ia Control Button Probe LEDs Figure 4 7 Control Button and Probe L
35. ce 92 298 124 298 TTV excised in 92 7 cm 69 9 cm p 0 0031 the primary lumpectomy procedure cm Unadjusted analysis Of the endpoints listed the clinically relevant endpoint of re excision procedure rate showed a 5 percentage point reduction in the SOC Device arm versus SOC arm The reoperation procedure rate is further described in Table 2 21 Note that fewer patients in the SOC Device arm required a second operation 71 patients in the SOC Device arm versus 85 patients in the SOC arm Recall that the MarginProbe device was only used during the initial lumpectomy operation and not during reoperations More patients in the SOC Device arm versus the SOC were converted to mastectomy There are numerous reasons for conversion to mastectomy and therefore this finding cannot be directly attributable to device use Table 2 21 Reoperation Procedure Rate Re excision including conversion to mastectomy Lumpectomy Additional Resections Total p Value Procedure 1 2 3 4 71 i 2 62 7 2 AOS ve 23 8 0 3177 85 SOC 298 11 7 1 28 5 Conversion to mastectomy in device arm 18 298 p 0 46 Conversion to mastectomy in control arm 13 298 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 20 MARGINPROBE User Manual Safety amp Regulatory Issues The following additional analyses Table 2 22 and Table 2 23 provide information r
36. ce Cleaning with the system turned on may be hazardous to the operator and or destructive to the system Exterior Cleaning The outer surface of the system may be wiped clean with a soft cotton cloth dipped in a mild soap and water solution Interior Inspection Any interior inspection should be performed only by Dune Medical authorized technical personnel Warning e The MARGINPROBE console generates hazardous voltages within the main console e The interior of the system may be serviced only by Dune Medical authorized technical personnel Service Information When communicating with Dune Medical representatives regarding the system always include the system model and serial number indicated on the console identification label located on the console s rear panel Warning MA Unauthorized servicing or modification of this system may expose the operator or patient to potential high voltage and radiofrequency hazards Note Note l Siis Improper use or maintenance of this system may invalidate the service warranty agreement Questions or problems should be referred to your Dune Medical representative or to the Service Center at e mail service dunemedical com Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 6 1 MARGINPROBE User Manual Maintenance Storage Do not store the MARGINPROBE system or the sterile probes wh
37. cococccinncccccnnononcccncnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnannnnnns 5 9 Figur 5 9 Measurement RESUS cuicos dada ida tr s 5 11 Figure S 10 Sereen Serling ia diodo indie eevabiect navies indie dai iO 5 11 Figure 95 11 Shutdown Message cid a eee eel ed 5 13 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Before You Start 1 BEFORE YOU START Warning e Read this manual to become familiar with all operating procedures and clinical requirements before attempting to operate the system e The MARGINPROBE system may be serviced only by Dune Medical Devices qualified personnel Conventions Used in this Manual The following conventions in the form of notes cautions and warnings are used in this manual Note ee The content of this Note offers general information that is important to keep in mind Caution A Caution alerts the user to the possibility of a potentially hazardous situation which if not avoided may result in minor or moderate injury to the user or damage to the equipment Warning A Warning alerts the user to the possibility of injury death or serious adverse reactions associated with the use or misuse of the system
38. ctive diagnostic tool for identification of cancerous tissue at the margins lt 1mm of the main ex vivo lumpectomy specimen following primary excision and is indicated for intraoperative use in conjunction with standard methods such as intraoperative imaging and palpation in patients undergoing breast lumpectomy surgery for previously diagnosed breast cancer Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 1 MARGINPROBE User Manual Safety amp Regulatory Issues Warnings Precautions and Contraindications Contraindications The Dune MARGINPROBE System should not be used To replace standard tissue histopathology assessment On ex vivo lumpectomy specimens that have been exposed to saline ultrasound gel or local anesthetic solutions On in vivo tissue i e it should not be used within the lumpectomy cavity On tissues other than breast tissue i e it should not be used on Sentinel Lymph Nodes Closer than 1 5 mm to a fine needle localization guidewire Warnings The MARGINPROBE should be used on tissue specimens within 20 minutes of excision The MARGINPROBE should not be used in patients who undergo full cavity excision following removal of the main lumpectomy specimen during the initial lumpectomy procedure The MARGINPROBE has not been studied in patients with Multicentric disease histologically diagnosed cancer in two different quadrants of the breast
39. during which a Calibrating message and progress bar appear at the bottom of the screen Figure 5 4 The calibration process takes approximately 10 seconds during which all the LEDs are illuminated In the event of a calibration failure a popup message will appear on the screen asking to press the probe s button while holding the probe in the air A second calibration failure will require replacement of the probe Calibrating Figure 5 4 Calibrating Message If the system is restoring the operation of a used probe the same calibrating message will appear on the screen When this occurs the calibrating message will appear and all the LEDs will turn on Resuming operation after Standby mode will also trigger calibration Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 4 MARGINPROBE User Manual Operating Instructions Probe Identification After the calibration process the probe type is determined by its ID microchip The system will be ready to measure the specimen immediately after calibration Figure 5 5 Ready for measurement Ready for measurement Figure 5 5 New Probe Screen You should connect a used probe only when restoring an ongoing procedure e g if the system was turned off and had to be restarted in the middle of an operation such as in the event of a power failure etc Note re e When connecting a probe to the console the system iden
40. e Control Rollin Phase n Mean SD n Meam SD n Mean SD n Mean SD Specimen Parameter Weight g 1000 6 6 6 8 329 7567 219 6062 1548 6760 Volume cm 1044 7 9 10 7 344 9 1 10 1 252 74 82 1640 81 102 Difference between weight and volume in number of margins is due to missing data Source Statistical Table M 54 in Appendix 10 2 2 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 17 MARGINPROBE User Manual Safety amp Regulatory Issues F Study Results 1 Safety Results 14 adverse events AEs were reported all being categorized as serious adverse events SAEs per study protocol definition One SAE was possibly related to the study device a wound infection requiring hospitalization and treatment with antibiotics Table 2 18 Frequency of Serious All Adverse Events by System Organ Class Preferred Term and Treatment Group Treatment Group Control Roll In Phase System Organ N 298 N 298 N 68 Class Preferred ON N N Term SAEs Pe ee Patients S Es Patients S gt zZ gt Z Es Procedural pain 0 0 1 1 0 Neoplasms Any benign malignant ane 1 1 0 0 0 unspecified incl cysts Uterine and polyps __ leiomyoma 1 1 0 0 0 0 1 0 0 0 1 1 0 Patients fw o o ose s 59 3 4 2 2m i 10 26 0 0 o Low i 1m tonsillitis 1 1
41. e in Device arm the proportion of No Otherwise de Re excision AVS analysis set Number of repeated ipsilateral breast surgical procedures Procedure Rate including mastectomies for each patient This endpoint Compared the was counted as an integer per patient the count was increased by 1 with each subsequent surgery Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 11 MARGINPROBE User Manual repele Population Safety amp Regulatory Issues Analysis Scoring Positive Margin AVS analysis set Presence Compared the groups using a Poisson regression model TTV excised in NSS analysis set the primary lumpectomy Compared the procedure cm groups using a 2 sided Wilcoxon Rank Sum Test Scored dichotomously Yes If there was at least 1 positive margin with d lt 1 mm after the first lumpectomy No Otherwise Total amount of tissue excised during lumpectomy for each patient The margin level and patient level ignoring location sensitivity and specificity are reported for diagnostic performance of the MarginProbe device These were not pre specified in terms of an acceptable minimal sensitivity and specificity The results here are based on the observed performance in the clinical pivotal study B Subject Accountability A total of 664 patients who were eligible for study enrollment underwent surgery and were allocated
42. e device procedures training or randomized were certified in device use 3 Pathology Protocol Pathological assessment was standardized and identical for both study arms Pathologists were blinded to randomization A positive margin was to be defined in this study as a margin microscopically measured and reported in the histopathology report to have cancer within 1 mm or less of the inked surface Each investigational site performed the histopathology assessment using a Standard Operating Procedure Re cut slides from the first 4 patients at each investigational site Training SOC or SOC Device were to be sent to a core lab and were to be used to review the accuracy and reporting capabilities of the investigational site pathology Dimensions L W D of all excised tissues were recorded Tissue volume was determined by use of the ellipsoid formula V 4 3 x L W D 4 Duration of Patient Follow up Patients were followed until the end of the lumpectomy procedure Data were collected regarding all ipsilateral breast surgical procedures and their respective permanent histopathology data Data were to be collected up until the earlier of the following events conversion to mastectomy initiation of chemotherapy or two months after the surgery date 5 Study Endpoints The prespecified study endpoints are as follows Safety evaluation consisted of assessment of all adverse events and serious adverse events which were summarized usi
43. e system a Connect Probe message will pop up on the screen Figure 5 1 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 1 MARGINPROBE User Manual Operating Instructions Connect Probe Figure 5 1 Connect Probe Popup Window The first screen that appears after initialization reflects the way the console was shut down in the previous session In case of a normal shutdown a clean screen without measurements will appear If the system was not shut down properly the screen will display all of the measurements from the previous session You can always toggle between a new screen and that of the previous session by a long press on the T button on the control panel pr If no action was taken for ten minutes the system will switch to Standby mode in which a screen saver will appear stating System in Standby Mode Figure 5 2 J Note Notef dd e Any popup displayed on the screen can be removed for ten seconds by pressing any of the buttons on the control panel or by a single click on the probe button e Resuming operation from Standby mode is done by pressing any of the buttons on the control panel or by a single click on the probe button DUNE Medical Devices MarginProbe in Standby Press any button to resume operation Figure 5 2 Standby Mode Message Caution Federal law restricts this device to sale by or on the order of a physician
44. egarding diagnostic performance of the device per margin and per patient ignoring location Table 2 22 Diagnostic Performance per margin Sensitivity Specificity PPV NPV7 95 CDi 95 Cl 95 Cl 95 Cl A 73 8 68 1 79 4 45 1 41 8 48 3 21 6 20 1 23 1 89 4 87 2 91 4 33 9 27 5 40 5 83 4 81 1 85 7 29 5 25 1 34 3 86 0 84 8 87 2 SOC Device 39 9 31 4 48 1 38 3 42 4 34 5 7 9 12 8 3 4 3 4 1 0 5 7 SOC Device pee 75 eae 3 80 5 46 4 ON 6 49 9 22 3 nan 7 23 8 90 1 88 0 92 Aa a oo a Ga 41 3 33 0 49 5 37 0 41 4 33 0 7 2 12 1 2 6 4 1 1 8 6 4 PPV and NPV calculated using Bayes theorem on sensitivity and specificity assuming a common prevalence across the two study arms of 17 0 195 Bootstrap percentile intervals tt There were 38 margins with a missing device reading 6 pathology positive margins and 32 pathology negative margins Table 2 23 Diagnostic Performance per patient ignoring location Sensitivity Specificity PPV NPV7 95 CI 95 CI 95 CI 95 CI oe 98 8 95 6 99 9 5 9 2 6 11 3 53 2 52 1 54 4 81 9 49 0 95 4 68 7 60 1 76 1 53 6 45 4 61 8 61 6 56 7 66 3 61 3 54 4 67 7 SOC Device 30 1 22 6 38 2 47 7 56 6 38 3 8 4 13 6 3 5 20 6 9 2 42 0 t SOC 96 3 92 2 98 6 8 9 4 7 15 0 53 4 51 9 54 9 68 9 46 2 85 2 68 7 60 1 76 1 53 6 45 4 61 8 61 6 56 7 66 3 61 3 54 4 67
45. epared according to the system dimensions presented in Figure 3 1 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 3 1 MARGINPROBE User Manual Console Placement Figure 3 1 System Dimensions Caution Do not cover the console when switched on Caution Federal law restricts this device to sale by or on the order of a physician PBO0501071 3 2 MARGINPROBE User Manual Console Placement Operational Environmental Requirements MARGINPROBE Operating Environment General Characteristics Temperature 15 C to 30 C 59 F to 86 F Humidity 30 to 80 at temperature lt 29 C 84 F Altitude 0 to 2000m 0 to 6560 feet Vibration 0 5G maximum 5Hz to 500HZ Storage Requirements MARGINPROBE Console Storage Environment General Characteristics Temperature 10 C to 40 C 50 F to 104 F Humidity 20 to 85 RH at temperature lt 40 C 104 F Altitude 0 to 4572m 0 to 15000 feet Vibration 0 5G maximum 5Hz to 500Hz Storage Requirements MARGINPROBE Probe e Use before the expiry date indicated on the label e Store at room temperature below 40 C 104 F in a dry place protected from light Console Placement Console Placement is carried out after uncrating the system from its crate to verify the system is ready for use in a surgical environment and it is performed by doing the fo
46. ere they may be exposed to heat direct sunlight water or any other liquids Ensure the console wheels are locked after positioning it in storage Environmental requirements during long term storage MARGINPROBE Console Temperature 10 C to 40 C 50 F to 104 F Humidity 20 to 85 RH at temperature lt 40 C 104 F Altitude 0 to 4572m 0 to 15000 feet Vibration 0 5G maximum 5Hz to 500Hz MARGINPROBE Probe Temperature lt 40 C 104 F Humidity 20 to 90 at temperature lt 40 C 104 F Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 6 2 MARGINPROBE User Manual Troubleshooting 7 TROUBLESHOOTING Introduction The MARGINPROBE system is equipped with self testing software routines that continuously monitor the systems operation If a system malfunction is detected an error message will appear on the screen The following troubleshooting guides do not attempt to list all possible system failures Any fault not listed should be referred to Dune Medical Service personnel Warning A Do not attempt to open or disassemble the system covers Troubleshooting Guides Table 7 1 provides a list of error messages that may appear on the screen their possible causes and corrective actions to be performed If the corrective actions listed in the table do not solve the problem contact your Dune Medical Service represen
47. esesenaaeeeeeees 1 1 2 Safety and Regulatory ISSUES accord alertar Ai 2 1 intended Use it tado aa wes eee 2 1 Warnings Precautions and Contraindications c ccccceceeeeeeceececeeeeeeeceeecaeaeeeeeeesesencaeaeeeeeeeeeeeenaeas 2 2 Potential Adverse Effects of the Device on Health c cccccecceeeeeeecceceeeeeeeesececaeeeeeeeeeseneecaeeeeeeeeeeeaea 2 3 Clinical Datak td 2 3 Electrical and Mechanical Safety Precauti0NS oooocccconnncccnonocicccononcnnccnnoncnc nano cnn cnnnn narran rar crnnr rca 2 34 Compliance with International Regulatory StandardS ooocoonnnnicinnnnicicinnoccccnnonnncnanancnn nan rca r canon 2 34 Device Regulatory Labels it inne heii ee li athe iia 2 35 Probe ldentification Label ica a ai 2 35 Console Identification Label c cccccceceeeeeeccceceeeee eee ceeeenaece cesses a a a aa a a 2 35 Electrical Hazard Kabel cists acide A ele de eee eee a 2 35 EtO Exposure Indicator cadena hadi aes ela A A A ond dae 2 35 3 Console Place Mesias a A dee ee eee 3 1 EU LNE ai E E adas 3 1 Facility REQUIFEMENS osai A ee ET A ch ee ee aa 3 1 Electrical Requirements A 3 1 SPAaCe REQUIFEMENIS E E cn ccesetacca gg ede a a id 3 1 Environmental Requirements MARGINPROBE dto arcos ide es 3 3 Storage Requirements MARGINPR BE Console raid 3 3 Storage Requirements MARGINPROBE Probe cuca da 3 3 GConsole Placement tors 24 imee Ai dt dt aden reed 3 3 A System Descrip acna ccuchu
48. essment versus a positive MarginProbe device reading and whether the shaving was taken before randomization or after specimen imaging While the device readings for each margin and the margins shaved were documented the timing of each shaving and the reason prompting the shaving was not collected Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 8 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 1 summarizes the strengths and limitations of the CSR primary effectiveness endpoint for the pivotal study Table 2 1 Strengths and limitations of the primary effectiveness endpoint CSR Strengths Limitations A focused assessment limited to what is The study design allows for an additional within the control of the MarginProbe option to perform cavity shavings in the device i e causing additional cavity SOC Device arm versus the SOC arm The shavings additional option in the SOC Device arm may be responsible for an increase in CSR in the SOC Device arm A by specimen assessment which does not The incremental contribution of the give partial credit to intraoperative re MarginProbe device to a higher CSR cannot exision of some positive margins on the be determined because the reason for taking a main specimen but not all positive margins cavity shaving i e SOC clinical suspicion on the main specimen or imaging versus a positive MarginProbe reading
49. face of fresh intact lumpectomy specimens The orientation of each measurement site was noted For each marked site the corresponding 7 mm wide tissue specimen was processed en face and microscopically evaluated as positive or negative for malignancy Figure 2 8 Study V Sampling Process A total of 175 subjects were enrolled in 3 sites during this study Surgeons at 2 institutions included in this study site 1 US site n 101 patients site 2 OUS site n 9 patients excised additional margins only where deemed necessary selective re excision Practice at the third institution US site n 65 patients 66 specimens was to routinely re excise all margins from the cavity total re excision While results from Study V served to further inform the MarginProbe product development Study V also serves to provide a comparison of differences in standard of care selective versus empiric total cavity shaving Patients who receive empiric routine re excision of all margins have greater conversion of initial positive lumpectomy margins to final negative margins The observed effect is illustrated below in Figures 2 9 and 2 10 comparing the final pathologies from patients treated at study sites 1 and 2 selective re excision versus study site 3 total re excision There is also literature see references list below suggesting that the standard empiric practice of complete partial lumpectomy cavity shavings in the same operative setting
50. ips or sutures Follow screen instruction and replace the probe if required If problem persists contact Dune Medical Hold the probe in the air and make sure the sensor is not covered Click the probe control button to restart calibration Follow screen instruction and replace the probe if required The initialization process does not start when turning on the console a progress bar does not appear on the screen Electronic malfunction Restart the system If problem persists contact Dune Medical Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 7 3 MARGINPROBE User Manual Troubleshooting Table 7 2 System Malfunction Troubleshooting Guide Continued Symptom Probable Cause Corrective Action Initialization process takes longer than usual progress bar is shown Internal modules are initializing Wait 5 minutes to complete initialization If problem persists restart the system If problem persists after restarting the system contact Dune Medical Measurement is not triggered upon coupling of probe to Vacuum airway is disconnected or Disconnect and reconnect the probe If problem persists restart the system If problem persists after restarting the system replace the probe ti damaged ISSUE If problem persists after replacing the probe contact Dune Medical System is not ready for
51. is console blinded intended use Positive margin identification fashion Assess guiding intraoperative resection cosmetic outcome is superior in Device SOC arm MAST associated with 60 compared to SOC 41 device use compared to SOC Cosmesis is not affected by device use Excised tissue volume is not affected by device Performance is the same for both palpable and non palpable lesions Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 25 MARGINPROBE User Manual The product development study results were used to develop the MarginProbe System Safety amp Regulatory Issues algorithm in the manner described in Figure 2 6 Algorithm Development Study Dates 3 2006 6 2007 6 2006 5 2008 11 2006 11 2007 10 2008 3 2010 Name Location Data Algorithm Patients Captured development in pathology Parameter selection Point data Specimen interior Algorithm working pt fine tune In OR Point data amp margin evaluation Specimen surface Vv US amp Israel N 175 VI Pilot MAST Israel N 143 In OR Margin evaluation Use by surgeon Algorithm working pt fine tune Pivotal US amp Israel Figure 2 6 Algorithm Development Process 1 Study HI Study III was conducted to create the classification database of actual tissue measurements using the MarginPro
52. ll in group This time includes surgical procedures resections completion of the protocol procedures and device use The mean duration of device use was 5 minutes for the Device group and 6 minutes for the Roll in group Table 2 13 presents the number and percent of patients with a palpable tumor excised during lumpectomy While all patients had non palpable lesions at screening inclusion criteria the lesion may or may not have been palpable in the ex vivo lumpectomy specimen There were no apparent differences between treatment groups with respect to palpable tumors during excision Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 15 MARGINPROBE User Manual Safety amp Regulatory Issues Table 2 13 Frequency Distribution of Palpable Tumor during Lumpectomy by Treatment Group Was The Tumor Palpable in Bere comi Y Roll In Phase The Excised Specimen N Patients N Patients N Patients 196 65 8 188 63 1 43 63 2 427 64 3 E 298 100 0 298 100 0 68 100 0 664 100 0 Source Statistical Table M 38 in Appendix 10 2 2 Various intraoperative evaluations were used at surgeon discretion in both the SOC and SOC Device arms and included radiological exam ultrasound ultrasonic guidance touch cytology gross assessment and frozen section The reason for performing a lumpectomy cavity shaving that is whether a shaving was prompted by gross
53. llowing 1 Unpack the console from its shipping crate 2 Check the console for external damage 3 Verify that the power cable is not damaged and matches the electrical wall socket connect it and ensure that it is firmly connected to the wall socket Note ee Do not attempt to connect the console to the electrical wall socket if the power cable s plug does not match the wall socket or if it is damaged 4 Plug the console s power cable into an appropriate electrical outlet 5 Turn on the main power switch Refer to Figure 3 2 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 3 3 MARGINPROBE User Manual Console Placement Figure 3 2 Electrical Connection 6 Turn on the console and wait for the connect probe message to be displayed on the screen Instructions can be found in chapter 5 Operating Instruction Preparing the System for Operation 7 The console is now ready for use 8 Turn off the console as described in chapter 5 System Shut Down Note we e Any damage to the packaging found prior to opening the package or to the console after opening the package should be reported to Dune Medical Devices e Incase a Please Contact Service message appears on the screen after turning on the console contact Dune Medical Devices Caution Federal law restricts this device to sale by or on the order of a physician
54. me excised MAST Study SOC 94 cm 95 Cl 83 15 104 08 1 Main Specimen Main Specimen Margin Status Margin Status 61 89 Shavings Shavings Not Shavings Shavings Not taken 47 taken 14 taken 47 taken 42 Histo Histo Histo Histo Histo Histo Margin on Margin on Margin on Margin on Margin Margin on Final Final Final Final on Final Final Pathology Pathology Pathology Pathology Pathology Pathology 23 24 14 3 44 42 Main Specimen Final Margin Totals 39 3 24 61 60 7 37 61 3 4 3 89 69 6 86 89 Figure 2 11 MAST Study Final Pathologies SOC Arm Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 32 MARGINPROBE User Manual SOC Device 143 MADT Study SOC Device Main Specimen Margin Status Safety amp Regulatory Issues Volume excised 107cm 95 Cl 93 84 119 64 AAA Main Specimen Margin Status 58 85 Shavings Shavings Not Shavings Shavings Not taken 55 taken 3 taken 77 taken 8 Histo Histo Histo Histo Histo Histo Margin on Margin on Margin on Margin on Margin Margin on Final Final Final Final on Final Final Pathology Pathology Pathology Pathology Pathology Pathology 30 25 3 2 75 8 Main Specimen Final Margin Totals 43 1 25 58 56 9 33 58 2 4 2 85 97 6 83 85 Figure 2 12 MAST Study Final Pathologies SOC Device Arm Caution
55. n a counter will appear on the screen indicating the number of measurements left 4 Note oe If eight consecutive failed measurements are obtained a message instructing the user to replace the probe will appear on the screen Caution A N If the probe tip is not lifted from the tissue after a measurement the system will continue to measure the same point repeatedly e Check the probe tip after measuring each margin gt If tissue remnants are found measure the margin again after wiping the probe tip e f measurements are taken by the probe without being coupled to tissue or if the sensor plate is found to be jammed a message instructing the user to replace the probe will appear on the screen e The probe is for single use only and must be disposed after each case Interpreting Measurement Results The device provides audible and visual indications regarding the assessment of tissue at each point measured Visual indication is by a colored bar on the screen that indicates a positive red or negative blue result Point and margin data accumulate on the screen Using the probe control button groups of points can be marked and oriented A margin with one or more positive points is indicated as a device positive margin and should be shaved from the cavity Device output is adjunctive to other information available intra operatively to guide the procedure Caution Federal law restricts this device to sale by
56. n Margin Margin on Final on Final Final Pathology Pathology Pathology 0 32 3 Main Specimen TR O o o Final Margin O ooo o o o S Totals 28 31 0 35 35 35 Figure 2 10 Study V Final Pathologies from Patients Treated at Study Site 3 Total Re excision Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 31 MARGINPROBE User Manual Safety amp Regulatory Issues 3 MAST Study This MAST pilot study was performed in Israel It was a prospective randomized controlled study designed to compared SOC lumpectomy with to SOC Device lumpectomy Three hundred subjects at 11 sites were enrolled n 149 device arm n 151 control arm The MAST study design was similar to the Pivotal study however there were some differences The MAST study involved a different MarginProbe device algorithm different device use instructions i e surgeons used the device at their discretion with respect to extent of device use and tissue targeted and were not required to act on positive MarginProbe device readings an assessment of post lumpectomy breast symmetry using a 4 point scale and intra operative pathology as part of SOC being used in approximately 20 of the cases The difference in protocols across studies may be reflected in the results of the SOC arm in the MAST Study compared to the pivotal IDE investigation The results are provided in Figures 2 11 and 2 12 below paces Volu
57. ncceuttaccegeraaadicaiehancceueth cageuk sendedvtaadaceisbenedegid a ea etlaaee 4 1 Introduction coastal lidia leticia lealtad 4 1 Console ciclos dial Rokl iabbectead lili 4 2 Control Panel EE cian tiras T E E dedo bit caida 4 3 Summary of control panel buttons ooooocccnnoccccnonacaccccononcncnanoncnn cano nan crnnn nana cnn nr 4 3 User Interface iii ti A a E a Ad eid E eed 4 4 Probe Component ds ee 4 5 Coupling and Measurement ccceeeeeeee cence ee eene ee nano nn ee ee eaeee ee eaeeeeeeaeeeeeeaaeeeeeeaeeeseenaeeeeneneeseeaes 4 6 Probe Control Buttons i 022g he ee een A ee ee eee ee 4 6 RrObe LEDS istic O NO 4 7 Probe Comme ctotie22 cis E O RT O 4 7 o Operating InstrUctionS itilii iaa 5 1 Introduction Econ coe seals O Sed dota idea neg seed deer 5 1 Preparing the System for Operation ooooonnnicccnnnnaccconnnonccnnnnorccnn nac cnn 5 1 Connect the Probe outside the Sterile Field oooooooocconnnnnnococncnnnnnnoconononcncnnnnnnnnnnoronncnnnnnnnnnnrncnncnnn 5 3 Operating tmie SyStem iss rent era a A i de eee ee 5 4 Probe Identifications ti A AS iia 5 5 Grouping Measurements According to MarginS ocoonnncccnnnncicccnnnocncccanonnnc nano nn nc nnno nn nr carr r cnn rca 5 6 Performing Measurements ica 5 8 Interpreting Measurement Results ooooonnnccccnnncocinnnnococcnnnononcnn nono nn crono rca r anna rra 5 10 Screen Scroll ic A A eee eect 5 11 Probe Usage Limitation eiociniciniaicc acid de dd ed ii 5
58. ng descriptive statistics The primary effectiveness endpoint CSR is measured as all pathologically positive margins on the main specimen being intraoperatively re excised or addressed A re Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 6 MARGINPROBE User Manual Safety amp Regulatory Issues excised or addressed margin does not mean that the final true outermost margin is pathologically negative for cancer A positive margin is defined as a margin microscopically measured and reported in the histology report to have cancer within 1 mm or less of the inked margin The main specimen is defined as the lumpectomy specimen removed prior to patient randomization The main lumpectomy specimen does not include additional shavings even if the cavity shaving was performed prior to patient randomization If a margin has been indicated as positive by the device and documented to not have been re excised as required by protocol due to resection already undermining the skin or reaching the pectoralis fascia this margin will be counted as detected and addressed for the purpose of CSR endpoint calculation although it was not re excised An illustration of how CSR is determined is provided in Figure 2 2 CSR 1 Effectiveness Endpoint CSR All positive margins on the main specimen being re excised addressed intraoperatively from positive main specimen cohor
59. ng the control button on the probe or the buttons on the control panel e Double clicking on the probe control button or pressing the button on the control panel opens a bracket e Double clicking again on the probe button after approving the group or pressing the button on the control panel closes the bracket e A pop up window will appear on the screen with the margin name in red Figure 5 6 Ready for measurement Figure 5 6 choosing the Margin to be measured Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 6 MARGINPROBE User Manual Operating Instructions Single click the control button to change the margin name and continue to single click until desired margin label is reached A bracket with a red letter above it indicating the margin name will also appear on the screen The letters correspond to the margins as follows e L Lateral e S Superior e M Medial e I Inferior e A Anterior e D Posterior Deep The margin names may also be changed by pressing the A or Y buttons on the control panel and scrolling to the desired margin label After choosing a margin name press and hold the probe control button to confirm the setting The letter above the bracket will turn yellow Figure 5 7 and measurements may be performed Margin confirmation may also be done from the console control panel by pressing the T button Ready for measurement Fig
60. nonnn nc nr nano narran rra 2 7 Figure 2 3 CSR and Clinical RelevanCe ooocccnnnnccinnnnococcnnnononcnnnono nano nnn ocn n ron nn nn r nora r rn rra 2 8 Figure 2 4 Pivotal Study Patient Flow Chart SOC Arm oooccccconacccccononcnccononcncnonannnccna non cn cnn non nncnnnnnnccnnnnns 2 22 Figure 2 5 Pivotal Study Patient Flow Chart SOC Device Arm oooonocccccnnoccccnononcncnononcncncnn cnn c nano ncnnnnns 2 23 Figure 2 6 Algorithm Development Proce oooccccconoccccccononccccononcnccnno conc nano ttrust turnat nnnn rra r ran Ennn atenua naten naat 2 26 Figure 2 7 Study Ill ROC curves of 3 different datasets ooocoonnncccinnncicccnocccccononcncnanannncncnno cnn r rana nn 2 28 Figure 2 8 Study V Sampling Process ooocccconnncccnnnocccccononcnccnnoncnc nano ncn cnn nan rca rca nn r narrar aana Aa rra 2 30 Figure 2 9 Study V Final Pathologies from Patients Treated at Study Sites 1 and 2 Selective Re E O O 2 31 Figure 2 10 Study V Final Pathologies from Patients Treated at Study Site 3 Total Re excision 2 31 Figure 2 11 MAST Study Final Pathologies SOC ArMooccccnnnccccccnnocccccononcnncnnoncnc nano nc nnn cano nc rra rca 2 32 Figure 2 12 MAST Study Final Pathologies SOC Device AlM ooooonccccnnonicccnnonccccnnoncncnnnan cnn r nana rancio 2 33 Figure S t System DIMENSIONS ecese inean e ERA craneales een 3 2 Figure 3 2 Electrical CONNECHON arreire esiaine iniedi iia tapi EENE AnA ANNAE EAA SAAE EAE AAEE AEEA 3 4 Figure 4 1
61. nts for Development Validation and Routine Control of a Sterilization Process for Medical Devices Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 34 MARGINPROBE User Manual Safety amp Regulatory Issues Device Regulatory Labels The following labels are affixed to the system and accessories Probe Identification Label The probe identification label located on the sealed pack includes the following information e Name and part number of the probe e Name and address of the manufacturer e Serial number lot number date of manufacture amp date of expiration e Cautionary symbol Single use only e Cautionary symbol Consult operating instructions e Cautionary symbol Do not use if sealed pack is compromised e Indicator that the probe has been sterilized by ethylene oxide Console Identification Label The console identification label located on the console s rear panel includes the following information e Name and address of the manufacturer e Name and model number and part number of the console e Date of manufacture and Serial number of the console e Electrical rating and fuse type definition e Cautionary symbol Follow operating instructions Electrical Hazard Label This label warns against dangerous electrical voltages within the console EtO Exposure Indicator This indicator found on the blister packaging of the probe is a chemically sensitive indicator
62. nts of the following TEC 60601 1 1990 Am A1 A2 Medical Electrical Equipment Part 1 General Requirements for Safety Collateral Standard Safety Requirements for Medical Electrical Systems IEC 60601 1 1 2001 Medical Electrical Equipment Part 1 1 General Requirements for Safety Collateral Standard Safety Requirements for Medical Electrical Systems IEC 60601 1 2 2001 Medical Electrical Equipment Part 1 2 General Requirements for Safety Collateral Standard Electromagnetic Compatibility Requirements And Tests IEC 60601 1 4 1996 Am Al Medical Electrical Equipment Part 1 4 General Requirements for Safety Collateral Standard Programmable Electrical Medical Systems IEC 60601 1 6 2004 Medical Electrical Equipment Part 1 6 General Requirements for Basic Safety and Essential Performance Collateral Standard Usability ISO 10993 1 2003 Biological Evaluation of Medical Devices Part 1 Evaluation and Testing ISO 10993 5 1999 Biological Evaluation of Medical Devices Part 5 Test for in vitro Cytotoxicity ISO 10993 7 2008 Biological Evaluation of Medical Devices Part 7 ETO Sterilization Residuals ISO 10993 10 2002 Biological Evaluation of Medical Devices Part 10 Tests for Irritation and Delayed Type Hypersensitivity ISO 10993 11 2006 Biological Evaluation of Medical Devices Part 11 Tests for Systemic Toxicity ISO 11135 1 2007 Sterilization of Health Care Products Ethylene Oxide Requireme
63. o detect extremely small differences in tissue characteristics In order to provide results as intended it is critical that the sensor be used in the manner validated during clinical development The performance of the device depends on carefully controlled manufacturing sterilization and calibration procedures The probe is designed and manufactured for single use The performance of the device cannot be guaranteed if not used in accordance with the instructions provided Clearing the Screen and Removing Popup Messages b d PTN The screen can be cleared at any point Press the T button to toggle between a clear screen and a screen showing the results up to the last measurement Any pop up displayed on the screen can be removed for ten seconds by pressing the A or Y buttons on the control panel or by single clicking the probe control button Standby Mode After ten minutes of inactivity the system will go into Standby mode and display a screen saver message System in Standby mode Press any button to resume operation Pressing any button on the control panel or the probe will clear the Standby screen message and set the system back to operational Ready mode During standby mode the pneumatic vacuum module will shut down A calibration process will automatically take place when resuming operation after Standby mode Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 12
64. o lumpectomy cavity e Was instructed not the use the MarginProbe device on ex vivo lumpectomy tissue that had been exposed to saline or ultrasound gel It was however acceptable to use the MarginProbe device on ex vivo lumpectomy tissue exposed to sterile water e Was instructed not to use the MarginProbe device in the 1 5 mm region of tissue surrounding a fine needle localization guidewire For both SOC and SOC Device arm patients lumpectomy specimens were imaged by ultrasound or radiography after randomization and device use Additional lumpectomy cavity re excisions were taken as deemed appropriate based on specimen imaging results Figure 2 1 provides a diagrammatic representation of the study design Note that the study design allows for an additional option to perform lumpectomy cavity shavings in the SOC Device arm option for shaving at 3 time points versus the SOC arm option for shaving at 2 time points Shaving option Shaving option Patient Enrollment Figure 2 1 Pivotal Study Design Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 5 MARGINPROBE User Manual Safety amp Regulatory Issues The MarginProbe device was not used during lumpectomy reoperations The study consisted of two phases a training phase and a randomization phase Each surgeon had to complete the training phase before being able to randomize patients Surgeons who had attended 2 or mor
65. ontaining cancers of all sizes down to 0 15 mm diameter features 165 cancerous sites from 50 patients and 588 nonmalignant sites Sensitivity 0 70 95 CI 0 63 0 77 Specificity 0 70 95 CI 0 67 0 74 The performance for different histopathology types are also summarized in Table 2 29 The two most common groups invasive ductal carcinoma IDC and ductal carcinoma in situ DCIS have sensitivities of 0 68 95 CI 57 77 and 0 63 95 CI 45 79 respectively Table 2 29 Study III Device Sensitivity for Different Histopathology Subgroups Number of Detected Detection rate Cancer histopathology samples 95 CI Infiltrating Ductal Carcinoma IDC 87 59 0 68 95 CI 57 77 Ductal Carcinoma in situ DCIS 35 22 0 63 95 C1 45 79 Infiltrating Lobular Carcinoma ILC 7 5 0 71 IDC DCIS 25 21 0 84 ILC DCIS 3 3 1 00 Other 8 6 0 75 Full dataset 165 116 0 70 Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 29 MARGINPROBE User Manual Safety amp Regulatory Issues 2 Study V Study V was a blinded study with MarginProbe System Type 1 0 device to assess performance of the device on the cut surface tissue of lumpectomy specimens as compared to histology Surgeons were blinded to the device outputs and could not act on device outputs The device measurements maximum of 20 were taken intraoperatively on the sur
66. or on the order of a physician PB0501071 5 10 MARGINPROBE User Manual Operating Instructions The visual results are shown on the screen Figure 5 9 e The red bars indicate a positive margin while the blue bars indicate a negative margin e The yellow brackets define a group and the letter or number above the bracket represents the group s label e The counter on the bottom left side of the screen indicates the number of measurements that were taken within the current group bracketed number and the total number of measurements taken from beginning of the session Ready for measurement Figure 5 9 Measurement Results Screen Scrolling Data points accumulate on the screen from left to right and top to bottom When the screen is full the rows will scroll upwards and data will continue to accumulate in the same manner Up to four rows will be displayed on the screen at any given time Once the screen is full with measurements the scrolling buttons will appear in the bottom right corner of the screen To view hidden rows scroll up or down by pressing the A or Y buttons on the control panel Figure 5 10 4 72 Ready for measurement Figure 5 10 Screen Scrolling Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 11 MARGINPROBE User Manual Operating Instructions Probe Usage Limitations The MARGINPROBE probe is a highly sensitive instrument designed t
67. s Ltd MARGINPROBE is a registered trademark of Dune Medical Devices Ltd All product names and any registered and unregistered trademarks mentioned in this manual that refer to goods or services offered by Dune Medical Devices Limited its subsidiaries and other affiliated companies are owned by Dune Medical Devices Ltd All third party product names and any registered or unregistered trademarks mentioned in this manual that refer to goods or services offered by parties other than Dune Medical Devices Limited remain the property of their respective owners User Manual Part Number PB0501071 Revision Level A Revision Date January 2013 This User Manual refers to MarginProbe System Model SA0580000 Contact information for equipment manufacturer and technical services Dune Medical Devices Inc 25 Thomson Place Suite 440 Boston Massachusetts 02210 USA Tel 1 508 620 2782 info dunemedical com Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 Page A MARGINPROBE User Manual This page is intentionally left blank Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 MARGINPROBE User Manual Table of Content TABLE OF CONTENTS A Before YOU adi dees in andere todas e la estos cda eta et Pat REE be 1 1 Conventions Used in this Manual ccccceceeeececceceeeeeeeeeeceaeeeeeeeeescceaeeeeeeeeeeseccacaeeeeee
68. s of the product development process as summarized in Table 2 25 None of these studies were pre approved by FDA Table 2 25 Summary of Developmental Clinical Studies Study Study Name Product Primary Objective Principal Results Number Subjects Description Point by point N 76 MarginProbe Obtain database set Device use has no permanent study in System and assess effect on tissue macroscopic or pathology Probe amp performance phase microscopic phase II MarginProbe II System Type Device performance per point m 3 2006 1 0 system on bread loafed lumpectomy console specimens sensitivity 100 and 6 2007 specificity 87 on homogeneous samples sensitivity 70 and specificity 70 on full dataset Intraoperative N 175 MarginProbe Assess intraoperative Even with a limited point blinded study System performance on the sampling by the device per phase II Probe amp resection surface of patient detection rate is superior Y MarginProbe lumpectomy with Device SOC 73 as 6 2006 System Type specimens and compared to SOC alone 46 1 0 system evaluate adjunctive 5 2008 console device contribution to SOC Pilot Study N 300 MarginProbe Assessment of Device is safe for System device detection intraoperative use 11 2006 Probe amp performance and 11 2007 MarginProbe clinical utility in a Re excision rate is reduced by System Type randomized 56 p 0 0027 1 0 system controlled patient
69. t PSS Positive margin Cancer within 1 mm or less of inked surface Figure 2 2 Illustration of CSR Primary Endpoint Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 7 MARGINPROBE User Manual Safety amp Regulatory Issues Figure 2 3 below illustrates how the CSR assessment includes both clinically relevant scenario which is the conversion of a specimen which has a pathologically positive for cancer margin to a specimen with negative for cancer margins and the clinically irrelevant scenario in which the additional shaving resulted in the true outermost margin of the specimen remaining pathologically positive for cancer Pivotal Study CSR 1 Effectiveness Endpoint Note The reason for taking a shaving is unknown Final or Final or True True Margin Margin stays Path converts to Positive Path Negative Fulfills CSR 1 effectiveness endpoint criterion Not Clinically Yes Clinically Relevant Relevant Figure 2 3 CSR and Clinical Relevance While CSR is a focused assessment that is limited to what is within the control of the MarginProbe device there are limitations to the CSR primary effectiveness endpoint Some of these limitations are present because the reason and timing for taking additional shavings of the lumpectomy cavity were not documented that is whether a shaving was taken because of clinical suspicion imaging other ass
70. tative Table 7 1 Error Message Troubleshooting Guide Error Message Probable Cause Corrective Action Temperature failure System will shutdown automatically Please contact service System s internal temperature has risen above 45 C 113 F Allow the system at least two minutes to cool down and then resume normal operation If problem persists contact Dune Medical Service Fan failure System will shutdown automatically Please contact service The system has detected a fatal failure in the heat dissipation fans Contact Dune Medical Service Fan problem detected Please notify service at end of procedure The system has detected a failure in the heat dissipation fans Continue normal operation and notify Dune Medical Service System Reached Max Number of Measurements Clear Screen The screen has displayed its maximal number of measurements Clear the screen long press on T button Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 7 1 MARGINPROBE User Manual Troubleshooting Table 7 1 Error Message Troubleshooting Guide continued Error Message Probable Cause Corrective Action Please shut system down and Restart The system has detected an internal error Shutdown and restart the system Resume normal operation If problem persists contact Dune Medical Service
71. tifies the probe and if the probe was used for a prior procedure an error message is displayed on the screen declaring the probe has exceeded its usage limit e Please refer to Table 7 1 Error message troubleshooting guide for a complete description of the messages displayed by the console iy The first displayed screen depends on how the system was shut down in the previous session If the system was not shut down properly the first screen will show the results of the previous session In all other cases the first screen will be blank To reach the desired screen to begin measuring press the T button for 3 seconds This will toggle between a clear screen and the screen showing the results of the previous session Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 5 MARGINPROBE User Manual Operating Instructions Note Note F e Ensure no previous records are displayed on the screen at the beginning of new procedure e By this point during surgery the surgeon has already removed and blotted the surgical specimen marked it for orientation and established the borders amp faces of the specimen Lateral Superior Medial Inferior Anterior and Posterior Deep Grouping Measurements According to Margins Point measurements per margin are grouped together within brackets which facilitates ease of review analysis The brackets may be opened and closed usi
72. tput and establish a routine protocol it is recommended to take measurements according to labeled specimen margins Performing Measurements Each individual measurement produces a binary positive negative display on the screen as well as an audio indication The volume of the audio indication may be adjusted by pressing the up down volume button on the control panel When pressing the up down volume button a beep will be heard The volume of the beep corresponds to the volume of the audio indication When the system is ready for measurement a partial vacuum is activated to aid in the initial coupling of the probe to the tissue surface Place the tip of the probe in contact with the tissue point to be measured and ensure that the entire tip is in contact with the tissue Figure 5 8 A measurement is automatically initiated when tissue to sensor coupling is achieved It is recommended to perform 5 to 8 measurements per margin up to 12 measurements on a large specimen In each measurement an area of 7 mm in diameter is sampled to the depth of at least 1 mm Note ee The specimen in Figure 5 8 is an artificial model for illustration purposes Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 8 MARGINPROBE User Manual Operating Instructions Figure 5 8 Probe Tip Application to the Specimen At the end of the measurement the vacuum is released and the pro
73. tudy Patient Flow Chart SOC Device Arm Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 23 MARGINPROBE User Manual Safety amp Regulatory Issues Summary of Supplemental Clinical Information A Pivotal Study Additional Analyses While not powered to detect differences across subpopulations there was a trend for outside of US patient populations to experience greater clinically relevant benefit than for the US population of patients enrolled as shown in Table 2 24 Table 2 24 Pivotal Study Results across Subpopulations US Patients Israel Patients n 566 n 98 Endpoint SOC SOC Device Device la MM 69 7 22 4 85 7 22 7 Incomplete 17 3 38 8 6 1 35 4 Surgical Re excision 2 Re excision 34 5 48 4 8 22 7 Procedure Rate Positive Margin 53 5 82 4 38 1 86 4 Presence Total Tissue Volume Excised cm Diagnostic Device SOC SOC SOC SOC Performance Device Device Sensitivity 73 4 87 8 95 CI 66 8 79 6 76 8 98 8 Specificity 44 7 e 9 95 CIT 40 8 48 8 e 0 62 0 Full detection is for Device not SOC Device arm 95 Bootstrap percentile intervals Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 2 24 MARGINPROBE User Manual Safety amp Regulatory Issues B Product Development Clinical Studies Product development clinical studies were conducted at various stage
74. und gel to the tissue before measurements are taken If necessary clean the surface of the tissue with sterile water An individual measurement is automatically performed by applying the probe tip perpendicular to the tissue and ensuring stable contact for the suction holes in the perimeter Once in contact with tissue the tip is automatically attached by slight suction and a measurement is taken Warning Z e Do not apply saline or ultrasound gel to the tissue before performing a measurement e Take measurements within 20 minutes after specimen excision Preparing the System for Operation Caution AN e Check the integrity of the screen at the start of every day s scheduled procedures Do not use the system if the screen is damaged e To prevent the system from tipping ensure that the wheel brakes are not locked when the system is in use Wheel brakes should only be engaged for storage of the console The MARGINPROBE system should be turned on and initialized prior to connection of the probe start shutdown switch on the control panel the power LED will turn green and the system will initialize its software while exhibiting a splash screen with the Dune Medical logo and an initialization progress bar Typical initialization time is around 3 minutes fe The power LED will be orange when the console is plugged in and turned off Press the When initialization is complete and a probe is not connected to th
75. ure 4 3 These controls will be described in detail in the Operating Instructions chapter section 5 p 5 1 Several of the functions performed from this panel may also be performed from the probe these will be explained in the Operating Instructions chapter Probe Connection Port MARGINPROBE Volume Up Down Controls Open Close Measurement Group Start Shutdo Edit Confirm y Measurement Switch Group Scrolling Control Group names Lines scrolling Figure 4 3 System Description Control Panel Summary of control panel buttons A full description of control panel buttons can be found in the chapter page 5 1 Caution Federal law restricts this device to sale by or on the order of a physician PBO0501071 4 3 MARGINPROBE User Manual System Description User Interface The user interface Figure 4 4 consists of an LCD screen and displays the system s status at any given point and the results of the measurements The user interface will be described in detail in the Operating Instructions chapter section 5 Ready for measurement Figure 4 4 Graphic User Interface Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 4 4 MARGINPROBE User Manual System Description Probe Components The probe is a hand held sterile disposable unit Figure 4 5 with a 3 year shelf life It includes the sensor FFS module attachment mechanism cali
76. ure 5 7 Confirmed Chosen Margin Note Note dd e Confirmation of margin label will take place automatically when measuring starts even if the control button was not pressed e To cancel measurement grouping in labeled brackets before obtaining any measurements first press and hold the button to approve the name and then double click to cancel the brackets Caution Federal law restricts this device to sale by or on the order of a physician PB0501071 5 7 MARGINPROBE User Manual Operating Instructions Grouping Measurements by Numbers groups may also be named by numbers instead of letters e g for measuring points on the specimen outside of the margin grouping framework To open a numbered group scroll to the numbers by pressing the probe control button or the A or Y buttons on the control panel Every time a group of measurements is closed the next numbered group created will be labeled by the next number Changing Frame Label can only be done before closing the brackets Changing the label is done by pressing and holding the probe control button to enable editing and scrolling by clicking to the desired label or by using the A or Y buttons on the control panel This can be done even if measurements were taken After the brackets have been closed changing the label is no longer possible Measurements can also be taken without grouping them by brackets Note Note In order to standardize device ou
77. vice to sale by or on the order of a physician PB0501071 7 2 MARGINPROBE User Manual Troubleshooting Table 7 2 lists some possible symptoms of system malfunctions for which no messages are displayed If the corrective actions listed in the tables do not solve the problem contact your Dune Medical Service representative Table 7 2 System Malfunction Troubleshooting Guide Symptom Probable Cause Corrective Action Un requested and or repetitive measurements when probe is not coupled to tissue Vacuum system openings at tip of probe are blocked Try to clear any visible tissue remnants that block the openings at the tip of the probe If problem persists replace probe and contact Dune Medical Measurement failure Note If eight consecutive failed measurements are obtained a message instructing the user to replace the probe will appear on the screen Calibration failure 1 Probe is lifted from tissue before beep is heard 2 Inadequate coupling of probe to tissue 3 Coupling obstacle wires clips or sutures present on specimen surface at point of measurement 4 Vacuum airway is disconnected or damaged Probe sensor plate may be covered or obstructed Leave probe coupled to tissue until beep is heard Ensure adequate coupling with proper suction by firmly holding probe tip perpendicular to tissue surface Assure that the probe tip is not placed over wires cl
78. y effective endpoint was based on PSS population and the secondary effectiveness endpoints were based on AVS PSS or NSS populations as shown in Tables 2 4 and 2 5 Table 2 4 The Primary Effectiveness Endpoints Population Analysis Endpoint Population Scoring CSR PSS analysis set Complete Surgical Re excision CSR was scored dichotomously as follows No At least one positive margin on the main specimen not re excised addressed intraoperatively Yes All positive margins on the main specimen re excised addressed intraoperatively Table 2 5 The Secondary Effectiveness Populations Endpoint Incomplete Surgical Re excision Analysis Population AVS analysis set The groups were compared using 2 sided Fisher s Exact Test Scoring Incomplete Surgical Re excision re excision is used to mean resection was scored dichotomously Yes If at least 1 positive margin with d lt 1 mm on the main specimen was not resected addressed intraoperatively No Otherwise This endpoint differed from the primary effectiveness endpoint Complete Surgical Resection since the Yes No definitions were opposite Full Detection PSS analysis set A 2 sided exact Scored dichotomously for SOC Device arm patients only Yes If all positive margins on the main specimen with d lt 1 groups using a Poisson regression model binomial 95 CI for mm were detected by the devic

User Manual - MarginProbe

Contents

Download Pdf Manuals

Related Search

Related Contents