(67 days)
The Intuitive Surgical Endoscopic Instrument Control System (da Vinci Surgical System, Models: IS4000 and IS4200) is intended to assist in the accurate control of Intuitive Surgical Endoscopic Instruments including rigid endoscopes, blunt and sharp endoscopic dissectors, scissors, scalpels, forceps/pick-ups, needle holders, endoscopic retractors, electrocautery and accessories for endoscopic manipulation of tissue, including grasping, cutting, blunt and sharp dissection, approximation, ligation, electrocautery, suturing, and delivery and placement of microwave and cryogenic ablation probes and accessories, during urologic surgical procedures, general laparoscopic surgical procedures, gynecologic laparoscopic surgical procedures, general thoracoscopic surgical procedures and thoracoscopically-assisted cardiotomy procedures. The system can also be employed with adjunctive mediastinotomy to perform coronary anastomosis during cardiac revasoularization. The system is indicated for adult and pediatric use. It is intended to be used by trained physicians in an operating room environment in accordance with the representative, specific procedures set forth in the Professional Instructions for Use.
This premarket notification is for a labeling modification only, to revise the Precaution for Representative Uses statement so that it does not apply to radical prostatectomy performed using the subject devices. This labeling change is supported by real-world evidence (RWE). There are no changes to the technological characteristics or the indications for use of the cleared da Vinci Xi or X Surgical Systems (Models IS4000 and IS4200) proposed in this submission. The da Vinci Xi and X Surgical Systems, Models IS4000 and IS4200, are software-controlled, electro-mechanical systems designed for surgeons to perform minimally invasive surgery. The Model IS4000 and Model IS4200 Surgical Systems consist of a Surgeon Console, a Patient Side Cart (PSC), and a Vision Side Cart (VSC) and are used with an Endoscope, EndoWrist Instruments, and Accessories.
The provided text describes a 510(k) premarket notification for a labeling modification to the da Vinci Xi and X Surgical Systems. The modification aims to remove a precaution statement regarding outcomes related to cancer treatment, specifically radical prostatectomy (RP), since this procedure was evaluated for overall survival. The submission relies on Real-World Evidence (RWE) from a retrospective cohort study to demonstrate the non-inferiority of robotic-assisted surgical device (RASD) radical prostatectomy compared to non-RASD RP concerning overall survival.
Here's a breakdown of the requested information based on the provided document:
1. Table of Acceptance Criteria and the Reported Device Performance
| Acceptance Criteria (Non-Inferiority Margin) | Reported Device Performance (Adjusted OS difference and 95% CI) | Non-Inferiority p-value |
|---|---|---|
| Primary Endpoint: 5-year Overall Survival (OS) Non-inferiority margin: 2.0% (meaning RASD RP OS should not be more than 2% worse than non-RASD RP OS) | 0.20 (-0.46, 0.86) (RASD vs non-RASD RP) | <0.0001 |
| Secondary Endpoint: 6-year OS Non-inferiority margin: 2.0% | 0.64 (-0.15, 1.42) (RASD vs non-RASD RP) | <0.0001 |
| Secondary Endpoint: 7-year OS Non-inferiority margin: 2.0% | 1.09 (0.14, 2.04) (RASD vs non-RASD RP) | <0.0001 |
| Secondary Endpoint: 8-year OS Non-inferiority margin: 2.0% | 0.61 (-0.41, 1.64) (RASD vs non-RASD RP) | <0.0001 |
| Secondary Endpoint: 9-year OS Non-inferiority margin: 2.0% | 0.76 (-0.41, 1.94) (RASD vs non-RASD RP) | <0.0001 |
| Secondary Endpoint: 10-year OS Non-inferiority margin: 2.0% | 0.88 (-0.35, 2.11) (RASD vs non-RASD RP) | <0.0001 |
Conclusion: For all evaluated time points (5, 6, 7, 8, 9, and 10 years), the p-value for non-inferiority was less than 0.0001. The adjusted overall survival difference (RASD vs non-RASD RP) and its 95% confidence interval were consistently within the non-inferiority margin of 2.0%. This indicates that robotic-assisted radical prostatectomy demonstrated non-inferiority to non-RASD RP with respect to overall survival.
2. Sample size used for the test set and the data provenance
- Sample Size (Primary Analysis): N = 24,350 patients (18,949 RASD RP, 5,401 Non-RASD RP)
- Sample Size (Sensitivity Analysis): N = 45,215 patients
- Country of Origin: United States
- Retrospective or Prospective: Retrospective cohort study
- Data Provenance: Secondary administrative healthcare claims data from Optum Clinformatics Data Mart (CDM), which is de-identified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This study used administrative healthcare claims data for overall survival (death events). The ground truth for death events would be derived directly from the claims data (e.g., death records), not from expert consensus or review of images by qualified experts. Therefore, this question is not applicable in the context of this study.
4. Adjudication method for the test set
Not applicable. The study utilized administrative claims data to determine death events, which are typically recorded facts within such datasets, rather than requiring adjudication of interpretations from multiple reviewers.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, an MRMC comparative effectiveness study was not done. This study is not evaluating an AI device for diagnostic or interpretative tasks where human readers' performance would be assessed with and without AI assistance. Instead, it is an effectiveness study comparing surgical approaches (RASD vs. non-RASD) on a clinical outcome (overall survival).
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. This study evaluates the effectiveness of a surgical system (da Vinci Xi/X) used by surgeons, not a standalone algorithm. The device, in this context, is the surgical system itself.
7. The type of ground truth used
The ground truth used was outcomes data, specifically the occurrence of a death event to determine overall survival. This information was extracted from de-identified administrative healthcare claims data.
8. The sample size for the training set
This study is a non-inferiority comparison of surgical approaches using real-world data; it does not describe the development or training of a specific algorithm within the da Vinci Surgical System itself. The surgical system is already cleared, and this submission is for a labeling change supported by clinical outcomes data. Therefore, the concept of a "training set" in the context of machine learning model development is not directly applicable to this study as described. The study used its entire dataset (N=24,350 for primary analysis, N=45,215 for sensitivity) to compare the efficacy of two surgical methods. Propensity score (PS) methods were used for statistical adjustment, which involves modeling the probability of receiving a treatment based on observed covariates, but this is a statistical technique, not an AI model training process in the typical sense for a new device submission.
9. How the ground truth for the training set was established
As explained in point 8, this study does not describe the training of a new AI algorithm. The ground truth for the outcomes (overall survival) was established through de-identified administrative healthcare claims data from Optum Clinformatics Data Mart (CDM).
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image contains two logos. On the left is the Department of Health & Human Services logo. On the right is the FDA logo, which includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
May 24, 2024
Intuitive Surgical Emily Hovick Senior Regulatory Affairs Specialist 1266 Kifer Road Sunnyvale, California 94086
Re: K240723
Trade/Device Name: da Vinci Xi Surgical System (IS4000); da Vinci X Surgical System (IS4200) Regulation Number: 21 CFR 876.1500 Regulation Name: Endoscope and accessories Regulatory Class: Class II Product Code: NAY Dated: March 15, 2024 Received: March 18, 2024
Dear Emily Hovick:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
{1}------------------------------------------------
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely, Digitally signed by Mark Mark Trumbore -S Trumbore -S Date: 2024.05.24
19:50:55 -04:00: Mark Trumbore, Ph.D. Assistant Director DHT4A: Division of General Surgery Devices OHT4: Office of Surgical and Infection Control Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
{2}------------------------------------------------
Indications for Use
Submission Number (if known)
Device Name
da Vinci Xi Surgical System (IS4000); da Vinci X Surgical System (IS4200)
Indications for Use (Describe)
The Intuitive Surgical Endoscopic Instrument Control System (da Vinci Surgical System, Models: IS4000 and IS4200) is intended to assist in the accurate control of Intuitive Surgical Endoscopic Instruments including rigid endoscopes, blunt and sharp endoscopic dissectors, scissors, scalpels, forceps/pick-ups, needle holders, endoscopic retractors, electrocautery and accessories for endoscopic manipulation of tissue, including grasping, cutting, blunt and sharp dissection, approximation, ligation, electrocautery, suturing, and delivery and placement of microwave and cryogenic ablation probes and accessories, during urologic surgical procedures, general laparoscopic surgical procedures, gynecologic laparoscopic surgical procedures, general thoracoscopic surgical procedures and thoracoscopically-assisted cardiotomy procedures. The system can also be employed with adjunctive mediastinotomy to perform coronary anastomosis during cardiac revasoularization. The system is indicated for adult and pediatric use. It is intended to be used by trained physicians in an operating room environment in accordance with the representative, specific procedures set forth in the Professional Instructions for Use.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
r-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
510(k) Summary (21 CFR § 807.92)
Submitter Information I.
| 510(k) Owner: | Intuitive Surgical, Inc.1266 Kifer RoadSunnyvale, CA 94086 |
|---|---|
| Contact Person: | Emily HovickSenior Regulatory Affairs SpecialistPhone: 314-359-8534Email: Emily.hovick@intusurg.com |
| Date Summary Prepared: | March 15, 2024 |
| II. Subject Device | |
| Trade Name: | da Vinci Xi Surgical Systemda Vinci X Surgical System |
| Common Name: | System, surgical, computer-controlled instrument |
| Classification: | Class II |
| Regulation: | 21 CFR § 876.1500, Endoscope and Accessories |
| Product Code: | NAY |
| III. Predicate Device Information | |
| Predicate Devices: | da Vinci Xi Surgical System, K131861 |
| da Vinci X Surgical System, K171294 |
IV. Device Description
This premarket notification is for a labeling modification only, to revise the Precaution for Representative Uses statement so that it does not apply to radical prostatectomy performed using the subject devices. This labeling change is supported by real-world evidence (RWE). There are no changes to the technological characteristics or the indications for use of the cleared da Vinci Xi or X Surgical Systems (Models IS4000 and IS4200) proposed in this submission. The da Vinci Xi and X Surgical Systems, Models IS4000 and IS4200, are software-controlled, electro-mechanical systems designed for surgeons to perform minimally invasive surgery. The Model IS4000 and Model IS4200 Surgical Systems consist of a Surgeon Console, a Patient Side Cart (PSC), and a Vision Side Cart (VSC) and are used with an Endoscope, EndoWrist Instruments, and Accessories.
Image /page/3/Picture/8 description: The image shows the word "INTUITIVE" in blue font. There is a small circle above the letter "U". The font is simple and sans-serif. The word is centered in the image.
{4}------------------------------------------------
V. Indications for Use
The Intuitive Surgical Endoscopic Instrument Control System (da Vinci Surgical System, Models: 134000 and IS4200) is intended to assist in the accurate control of Intuitive Surgical Endoscopic Instruments including rigid endoscopes, blunt and sharp endoscopic dissectors, scalpels, forceps/pick-ups, needle holders, endoscopic retractors, electrocautery and accessories for endoscopic manipulation of tissue, including grasping, cutting, blunt and sharp dissection, approximation, ligation, electrocautery, suturing, and delivery and placement of microwave and cryogenic ablation probes and accessories, during urologic surgical procedures, general laparoscopic surgical procedures, gynecologic laparoscopic surgical procedures, general thoracoscopic surgical procedures and thoracoscopically-assisted cardiotomy procedures. The system can also be employed with adjunctive mediastinotomy to perform coronary anastomosis during cardiac revascularization. The system is indicated for adult and pediatric use. It is intended to be used by trained physicians in an operating room environment in accordance with the representative, specific procedures set forth in the Professional Instructions for Use.
Precaution for Representative Uses
The demonstration of safety and effectiveness for the representative specific procedures did not include evaluation of outcomes related to the treatment of cancer (overall survival, disease-free survival, local recurrence), except for radical prostatectomy which was evaluated for overall survival, or treatment of the patient's underlying disease/condition. Device usage in all surgical procedures should be guided by the clinical judgment of an adequately trained surgeon.
VI. Technological Characteristics
This premarket notification is for a change to the labeling only. There are no changes to the technological characteristics of the cleared da Vinci Xi or X Surgical Systems (Models IS4000 and IS4200) proposed in this submission. The da Vinci Xi and X Surgical Systems, Models IS4000 and IS4200, are softwarecontrolled, electro-mechanical systems designed for surgeons to perform minimally invasive surgery. The Model IS4000 and Model IS4200 Surgical Systems consist of a Surgeon Console, a Patient Side Cart (PSC), and a Vision Side Cart (VSC) and are used with an Endoscope, EndoWrist Instruments, and Accessories.
VII. Performance Data
There are no changes to the technological characteristic of the subject device in this premarket notification. Therefore, no bench or preclinical data were required.
Image /page/4/Picture/10 description: The image shows the word "INTUITIVE" in blue font. There is a small circle above the letter "U". The font is sans-serif and the letters are evenly spaced. The background is white.
{5}------------------------------------------------
Clinical Data Summary
Table 1: Study Summary
| Title | Use of Real-World Data to Demonstrate That Overall Survival Following Robotic-Assisted Radical Prostatectomy is Non-Inferior to Non-Robotic Assisted RadicalProstatectomy |
|---|---|
| Study Objective | Primary objective: Evaluate non-inferiority of robotic-assisted surgical device(RASD) radical prostatectomy (RP) as compared with non-RASD RP with respectto the difference in probability of 5-year overall survival (OS) among male patientsat least 35 years of age with treatment-naive prostate cancer. |
| Secondary objectives: Evaluate non-inferiority of RASD RP as compared withnon-RASD RP with respect to the difference in 6-year, 7-year, 8-year, 9-year, and10-year probability of OS among male patients at least 35 years of age withtreatment-naive prostate cancer. | |
| Study Design | A retrospective cohort study using secondary administrative healthcare claims datato evaluate OS following RP performed via RASD as compared to non-RASDopen surgical approaches among patients with treatment-naive prostate cancer inthe United States. |
| StudyPopulation | Male patients at least 35 years of age with treatment-naive prostate cancerundergoing a RASD versus non-RASD RP procedure. |
| Number ofPatients / TimePeriod | Primary analyses: N = 24,350 patients with an RP procedure between July 2007and December 2014, restricting the last procedure date to occur 5 years prior to thestart of COVID-19.Sensitivity analyses: N = 45,215 patients with an RP procedure between July 2007and December 2020, utilizing all available data. |
| Data Source | Optum Clinformatics Data Mart (CDM) de-identified administrative healthcareclaims data |
| StudyEndpoints | Primary endpoint: The difference in the probability of OS at 5 years after the RPprocedure (i.e., the difference in the percent of patients who do not have a deathevent), comparing RASD RP to non-RASD RP.Secondary endpoints: The difference in the probability of OS at 6, 7, 8, 9, and 10years after the RP procedure, comparing RASD RP to non-RASD RP. |
| StatisticalMethods | Propensity score (PS) method with stratification was applied on the outcome-freedesign. The overall survival rate was estimated based on Average Treatment Effectamong the Treated population. |
Image /page/5/Picture/5 description: The image shows the word "INTUITIVE" in blue font. There is a small circle above the "U" in the word. The font is sans-serif and the letters are evenly spaced.
{6}------------------------------------------------
Table 2: Baseline characteristics of patients with treatment-naive prostate cancer undergoing radical prostatectomy procedure between 7/1/2007 and 12/31/2014, by surgical approach, before and after PS stratification. Note: subgroup analyses were not performed for any endpoint.
| Before PS Stratification | After PS stratification (weighted N, by strata) | ||||||
|---|---|---|---|---|---|---|---|
| RASD RPN = 18,949 | Non-RASD RPN = 5,401 | ASD | RASD RPWeighted N =3,850.31 | Non-RASD RPWeighted N = 1,019.69 | ASD | ||
| Demographics [Day 0] | |||||||
| Age in years at index | 0.020 | 0.040 | |||||
| mean (SD) | 60.94 (7.29) | 61.06 (7.27) | 61.12 (3.28) | 61.12 (3.29) | |||
| median [IQR] | 61.00 [56.00,66.001 | 61.00 [56.00, 66.00] | 61.22 [56.00, 66.22] | 61.22 [55.81, 66.42] | |||
| Age categories, years | |||||||
| 35 - 44 | 235 (1.24%) | 68 (1.26%) | 0.000 | 47.6 (1.24%) | 12.9 (1.23%) | 0.060 | |
| 45 - 54 | 3,522 (18.59%) | 996 (18.44%) | 0.000 | 716.3 (18.59%) | 187.7 (18.06%) | 0.030 | |
| 55 - 64 | 8,799 (46.44%) | 2,497 (46.23%) | 0.000 | 1,786.3 (46.43%) | 472.4 (46.97%) | 0.040 | |
| 65 - 74 | 6,000 (31.66%) | 1,734 (32.11%) | 0.010 | 1,220.2 (31.67%) | 325.7 (31.37%) | 0.030 | |
| >75 | 393 (2.07%) | 106 (1.96%) | 0.010 | 79.9 (2.08%) | 21.0 (2.37%) | 0.040 | |
| Race/Ethnicity; n (%) | |||||||
| Asian | 386 (2.04%) | 94 (1.74%) | 0.020 | 80.3 (2.04%) | 18.5 (2.01%) | 0.030 | |
| Black | 1,787 (9.43%) | 597 (11.05%) | 0.050 | 352.5 (9.43%) | 109.4 (9.78%) | 0.030 | |
| Hispanic | 1,061 (5.60%) | 338 (6.26%) | 0.030 | 211.1 (5.6%) | 61.8 (5.42%) | 0.040 | |
| White | 14,713 (77.65%) | 4,057 (75.12%) | 0.060 | 3,007.3 (77.64%) | 771.8 (77.51%) | 0.020 | |
| Unknown | 1,002 (5.29%) | 315 (5.83%) | 0.020 | 199.1 (5.29%) | 58.3 (5.28%) | 0.010 | |
| Region; n (%) | |||||||
| Midwest | 1,676 (8.84%) | 413 (7.65%) | 0.040 | 348.0 (8.85%) | 81.2 (9.11%) | 0.050 | |
| Northeast | 5,026 (26.52%) | 1,495 (27.68%) | 0.030 | 1,015.6 (26.52%) | 278.9 (26.41%) | 0.030 | |
| South | 8,349 (44.06%) | 2,248 (41.62%) | 0.050 | 1,711.5 (44.06%) | 430.2 (43.89%) | 0.030 | |
| West | 3,898 (20.57%) | 1,245 (23.05%) | 0.060 | 775.2 (20.57%) | 229.4 (20.59%) | 0.030 | |
| Insurance type; n (%) | |||||||
| Commercial | 14,052 (74.16%) | 4,111 (76.12%) | 0.050 | 2,838.4 (74.16%) | 771.0 (74.41%) | 0.030 | |
| Medicare | 4.897 (25.84%) | 1,290 (23.88%) | 0.050 | 1,011.9 (25.84%) | 248.7 (25.59%) | 0.030 | |
| Year of RP procedure; n (%)2007 | |||||||
| 2008 | 998 (5.27%)2,343 (12.36%) | 715 (13.24%)1,150 (21.29%) | 0.2800.240 | 157.8 (5.27%)401.4 (12.37%) | 112.4 (5.98%)192.0 (11.96%) | 0.020 | |
| 2009 | 2,702 (14.26%) | 955 (17.68%) | 0.090 | 517.0 (14.26%) | 177.4 (14.34%) | 0.0400.030 | |
| 2010 | 2,584 (13.64%) | 805 (14.90%) | 0.040 | 509.3 (13.64%) | 155.2 (13.83%) | 0.030 | |
| 2011 | 2,968 (15.66%) | 672 (12.44%) | 0.090 | 624.8 (15.66%) | 139.1 (15.80%) | 0.020 | |
| 2012 | 2,506 (13.22%) | 431 (7.98%) | 0.170 | 550.5 (13.23%) | 93.6 (13.52%) | 0.050 | |
| 2013 | 2,546 (13.44%) | 376 (6.96%) | 0.220 | 569.5 (13.44%) | 83.4 (13.33%) | 0.020 | |
| 2014 | 2,302 (12.15%) | 297 (5.50%) | 0.240 | 520.2 (12.15%) | 66.5 (11.25%) | 0.040 | |
| Comorbidities and clinical characteristics [Day -180, | |||||||
| Day 0] | |||||||
| Evidence of smoking or smoking cessation; n (%) | 4,646 (24.52%) | 1,287 (23.83%) | 0.020 | 948.1 (24.52%) | 245.9 (24.98%) | 0.030 | |
| Alcohol related disorders; n (%) | 31 (0.16%) | 7 (0.13%) | 0.010 | 6.5 (0.16%) | 1.4 (0.17%) | 0.020 | |
| Obesity; n (%) | 1,940 (10.24%) | 504 (9.33%) | 0.030 | 401.4 (10.24%) | 97.3 (10.28%) | 0.020 | |
| Cancers other than prostate cancer; n (%) | 1,575 (8.31%) | 577 (10.68%) | 0.080 | 306.1 (8.31%) | 104.0 (8.82%) | 0.030 | |
| Benign prostatic hyperplasia; n (%) | 637 (3.36%) | 187 (3.46%) | 0.010 | 129.3 (3.36%) | 35.1 (3.22%) | 0.040 | |
| Lower urinary tract conditions; n (%) | 7,206 (38.03%) | 2,248 (41.62%) | 0.070 | 1,441.4 (38.03%) | 417.2 (39.03%) | 0.040 | |
| Hypertension; n (%) | 11,671 (61.59%) | 3,412 (63.17%) | 0.030 | 2,361.3 (61.59%) | 641.3 (62.13%) | 0.020 | |
| Diabetes mellitus; n (%) | 3,168 (16.72%) | 932 (17.26%) | 0.010 | 640.5 (16.72%) | 175.6 (17.24%) | 0.030 | |
| Kidney disease; n (%) | 1,468 (7.75%) | 465 (8.61%) | 0.030 | 293.8 (7.75%) | 85.6 (7.77%) | 0.030 | |
| Gagne Comorbidity Index | 0.120 | 0.030 | |||||
| mean (SD) | 1.21 (1.45) | 1.39 (1.64) | 1.23 (0.63) | 1.23 (0.64) | |||
| median [IQR] | 1.00 [0.00, 1.00] | 1.00 [0.00, 2.00] | 1.00 [0.00, 1.55] | 1.00 [0.00, 1.77] | |||
| Frailty score | 0.110 | 0.040 | |||||
| mean (SD) | 0.10 (0.03) | 0.10 (0.03) | 0.10 (0.01) | 0.10 (0.01) | |||
| median [IQR] | 0.10 [0.08, 0.12] | 0.10 [0.08, 0.12] | 0.10 [0.08, 0.12] | 0.10 [0.08, 0.12] | |||
| Medications and treatments [Day -180, Day -1] | |||||||
| Pelvic or abdominal surgery; n (%) | 17,736 (93.60%) | 5,118 (94.76%) | 0.050 | 3,595.5 (93.6%) | 964.7 (93.97%) | 0.030 | |
| Transurethral prostate surgery; n (%) | 70 (0.37%) | 41 (0.76%) | 0.050 | 12.6 (0.37%) | 6.7 (0.4%) | 0.030 | |
| Urethral or bladder neck surgery; n (%) | 2,805 (14.80%) | 819 (15.16%) | 0.010 | 567.3 (14.8%) | 153.9 (15.01%) | 0.020 | |
| Treatment for other cancers: | |||||||
| Radiotherapy; n (%) | 13 (0.07%) | 7 (0.13%) | 0.020 | 2.2 (0.07%) | 1.2 (0.08%) | 0.020 | |
| Chemotherapy; n (%) | 8 (0.04%) | 5 (0.09%) | 0.020 | 1.4 (0.04%) | 0.8 (0.05%) | 0.000 | |
| Immunotherapy; n (%) | 0 (0.00%) | 0 (0.00%) | 0.000 | 0.0 (0%) | 0.0 (0%) | 0.000 | |
| Hormonal therapy; n (%)Anticoagulants; n (%) | 11 (0.06%)462 (2.44%) | 3 (0.06%)86 (1.59%) | 0.000 | 2.3 (0.06%)100.3 (2.44%) | 0.6 (0.05%)17.7 (2.32%) | 0.030 | |
| Antiplatelets (including aspirin); n (%) | 650 (3.43%) | 167 (3.09%) | 0.0600.020 | 134.3 (3.43%) | 32.5 (3.5%) | 0.0200.020 | |
| NSAIDs; n (%) | 2,679 (14.14%) | 745 (13.79%) | 0.010 | 546.5 (14.14%) | 141.3 (14.11%) | 0.020 | |
| Laboratory results [Day -180, Day -1] | |||||||
| Before PS Stratification | After PS stratification (weighted N, by strata) | ||||||
| RASD RPN = 18,949 | Non-RASD RPN = 5,401 | ASD | RASD RPWeighted N =3,850.31 | Non-RASD RPWeighted N = 1,019.69 | ASD | ||
| Preoperative PSA, ng/mL (last value observed, amongthose with ≥1 value) | 0.120 | 0.130 | |||||
| mean (SD) | 6.74 (6.43) | 7.84 (10.79) | 7.90 (2.87) | 7.90 (5.31) | |||
| median [IQR] | 5.24 [4.20, 7.30] | 5.42 [4.30, 8.00] | 5.49 [4.17, 7.23] | 5.49 [4.31, 7.96] | |||
| Among N with non-missing value | 4,567 | 1,020 | 956.10 | 199.90 | |||
| Preoperative PSA categories, ng/mL; n (%) | |||||||
| < 10 | 3,989 (21.05%) | 844 (15.63%) | 0.140 | 834.0 (21.05%) | 165.9 (18.23%) | 0.070 | |
| 10 - <20 | 461 (2.43%) | 133 (2.46%) | 0.000 | 97.3 (2.43%) | 25.7 (2.72%) | 0.030 | |
| ≥20 | 117 (0.62%) | 43 (0.80%) | 0.020 | 24.8 (0.62%) | 8.3 (0.85%) | 0.040 | |
| Missing | 14,382 (75.90%) | 4,381 (81.11%) | 0.130 | 2,894.2 (75.9%) | 819.8 (78.19%) | 0.050 | |
| Healthcare resource utilization [Day -180, Day -1] | |||||||
| Days hospitalized, among those with ≥0 hospitalizations | 0.010 | 0.030 | |||||
| mean (SD) | 0.27 (2.12) | 0.30 (2.82) | 0.26 (0.96) | 0.26 (0.85) | |||
| median [IQR] | 0.00 [0.00, 0.00] | 0.00 [0.00, 0.00] | 0.00 [0.00, 0.00] | 0.00 [0.00, 0.00] | |||
| Number of outpatient visits, among those with ≥0outpatient visits | 0.060 | 0.040 | |||||
| mean (SD) | 12.31 (6.32) | 11.95 (6.26) | 12.38 (2.88) | 12.38 (3.25) | |||
| median [IQR] | 11.00 [8.00, 15.00] | 11.00 [8.00, 14.00] | 11.07 [8.23, 14.88] | 11.07 [8.23, 14.68] |
INT
{7}------------------------------------------------
RASD = Robotic-assisted surgical device; RP = radical prostatedor; \QR = interquaritie rang; ; NSAD = non-steriodal anti-inflanmatory drug; ASD = absolute standardized difference
Bracketed date ranges describe the time period over assessed. Day O refers to the date of RP procedure, and date ranges with hard brackets are inclusive of start/end dates.
With the exception of age, PSA results, days hospited visits, which are reported as the mean (SD) and median (NR) for patients in each surgical approach group, characteristics are described a hith evidence of each characteristic during the specified assessment period and the percent of the bal number of patients within each treatment group, reported as n (%).
ASDs ≥ 0.1 have been bolded to indicate meaningful differences between groups.
Image /page/7/Picture/7 description: The image shows the word "INTUITIVE" in blue font. There is a small circle above the "U" in the word. The font is sans-serif and the letters are evenly spaced. The image is simple and clean, with a white background.
{8}------------------------------------------------
Table 3: Absolute differences in overall survival among patients with a radical prostatectomy procedure between 7/1/2007 and 12/31/2014, comparing patients with RASD RP vs. non-RASD RP, primary and secondary analyses.
| Analysis and treatment group | Total No. of patients in each group | Total No. of patients with a death event | Total No. of patients without a death event | Total No. of patients censored due to end of study period (12/31/2019)^ | Probability of OS and 95% CI (risk per 100 patients) | Unadjusted OS difference and 95% CI* (risk difference per 100 patients) RASD vs non-RASD RP | Adjusted OS difference and 95% CI* (risk difference per 100 patients) RASD vs non-RASD RP | Non-inferiority p-value** RASD vs non-RASD RP |
|---|---|---|---|---|---|---|---|---|
| Primary analysis: 5-year OS | ||||||||
| RASD RP | 18,949 | 734 | 18,215 | 0 | 96.13 (95.85, 96.40) | 0.48 (-0.13, 1.09) | 0.20 (-0.46, 0.86) | <0.0001 |
| Non-RASD RP | 5,401 | 235 | 5,166 | 0 | 95.65 (95.11, 96.19) | reference | reference | reference |
| Secondary analysis: 6-year OS | ||||||||
| RASD RP | 18,949 | 933 | 18,016 | 2,188 | 95.01 (94.69, 95.32) | 0.86 (0.16, 1.57) | 0.64 (-0.15, 1.42) | <0.0001 |
| Non-RASD RP | 5,401 | 314 | 5,087 | 286 | 94.14 (93.52, 94.77) | reference | reference | reference |
| Secondary analysis: 7-year OS | ||||||||
| RASD RP | 18,949 | 1,120 | 17,829 | 4,586 | 93.79 (93.44, 94.15) | 1.26 (0.47, 2.06) | 1.09 (0.14, 2.04) | <0.0001 |
| Non-RASD RP | 5,401 | 393 | 5,008 | 643 | 92.53 (91.82, 93.24) | reference | reference | reference |
| Secondary analysis: 8-year OS | ||||||||
| RASD RP | 18,949 | 1,309 | 17,640 | 6,904 | 92.33 (91.92, 92.73) | 1.34 (0.46, 2.23) | 0.61 (-0.41, 1.64) | <0.0001 |
| Non-RASD RP | 5,401 | 463 | 4,938 | 1,025 | 90.98 (90.20, 91.77) | reference | reference | reference |
| Secondary analysis: 9-year OS | ||||||||
| RASD RP | 18,949 | 1,462 | 17,487 | 9,632 | 90.79 (90.32, 91.26) | 1.51 (0.52, 2.49) | 0.76 (-0.41, 1.94) | <0.0001 |
| Non-RASD RP | 5,401 | 531 | 4,870 | 1,614 | 89.28 (88.42, 90.16) | reference | reference | reference |
| Secondary analysis: 10-year OS | ||||||||
| RASD RP | 18,949 | 1,578 | 17,371 | 11,961 | 89.18 (88.64, 89.73) | 1.87 (0.75, 2.99) | 0.88 (-0.35, 2.11) | <0.0001 |
| Non-RASD RP | 5,401 | 595 | 4,806 | 2,322 | 87.31 (86.34, 88.29) | reference | reference | reference |
RASD = Robotic-assisted surgical device; RP = radical prostatectomy; Cl = confidence interval; OS = overall surviva
Patients are followed from one day affer the intil the earliest occurrence of a recorded dealth the maximum follow-un period (5 years in the anaysis; 6, 7, 8, 9, and 10 years, respectively, in each of the spiral of 1231/2019 (prior to known increases in morally starting in 2020 due the COVD-19 partemin
^ Survival probabilities are calculated using a Kaplan-Meier approach to account for censoring
- 95% Cls are reported to aid interpretation but are distinct from non-inferiority hypothesis testing
** p-values correspond to hypothesis testing of RASD RP vs non-RASD RP yolere the non-inferiority margin is set o 2.0% and the significance level of the test is set at one-sided 0.025. A hierachical approach was used null hypothesis at a significance level of 0.025. No adjustment for multiple testing was conducted, given that null hypotheses were hieraritically ordered and the same PS quintles were used for all primary and secondary the primary endpoint (5year OS) was evaluated for statistical signify and evaluated only if the previous was found to be statistically significant. Had any endport been found to have p > 0.025. no subsequent endpoints would have been evaluated
VIII. Conclusion
RWE was provided to demonstrate that the retrospective clinical data met all overall survival endpoints. This supports the modification of the Precaution for Representative Uses statement so that it does not apply to RP performed using the subject devices. These data prove the utility of RWE in support of premarket submissions.
The observed all-cause mortality in this study is similar to rates found in a systematic literature review performed by FDA. Based on tipping-point analyses performed by FDA, more than 28% differential bias in all-cause mortality ascertainment between RASD arms of this study would be needed to alter the results of the primary non-inferiority analysis. Additionally, examination of the data did not suggest presence of differential bias in all-cause mortality ascertainment between RASD and non-RASD arms of this study.
§ 876.1500 Endoscope and accessories.
(a)
Identification. An endoscope and accessories is a device used to provide access, illumination, and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optical system for conveying an image to the user's eye and their accessories may assist in gaining access or increase the versatility and augment the capabilities of the devices. Examples of devices that are within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes, flexible or rigid choledochoscopes, colonoscopes, diagnostic cystoscopes, cystourethroscopes, enteroscopes, esophagogastroduodenoscopes, rigid esophagoscopes, fiberoptic illuminators for endoscopes, incandescent endoscope lamps, biliary pancreatoscopes, proctoscopes, resectoscopes, nephroscopes, sigmoidoscopes, ureteroscopes, urethroscopes, endomagnetic retrievers, cytology brushes for endoscopes, and lubricating jelly for transurethral surgical instruments. This section does not apply to endoscopes that have specialized uses in other medical specialty areas and that are covered by classification regulations in other parts of the device classification regulations.(b)
Classification —(1)Class II (special controls). The device, when it is an endoscope disinfectant basin, which consists solely of a container that holds disinfectant and endoscopes and accessories; an endoscopic magnetic retriever intended for single use; sterile scissors for cystoscope intended for single use; a disposable, non-powered endoscopic grasping/cutting instrument intended for single use; a diagnostic incandescent light source; a fiberoptic photographic light source; a routine fiberoptic light source; an endoscopic sponge carrier; a xenon arc endoscope light source; an endoscope transformer; an LED light source; or a gastroenterology-urology endoscopic guidewire, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.(2) Class I for the photographic accessories for endoscope, miscellaneous bulb adapter for endoscope, binocular attachment for endoscope, eyepiece attachment for prescription lens, teaching attachment, inflation bulb, measuring device for panendoscope, photographic equipment for physiologic function monitor, special lens instrument for endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and cleaning brush for endoscope. The devices subject to this paragraph (b)(2) are exempt from the premarket notification procedures in subpart E of part 807of this chapter, subject to the limitations in § 876.9.