# Summary of Safety and Effectiveness {#summary-of-safety-and-effectiveness .unnumbered}

## General Information

> **[Device Generic Name]{.underline}:** Cervical Interbody Fusion
> Instrumentation
>
> **[Device Trade Name]{.underline}:** BAK/Cervical Interbody Fusion
> System
>
> **[Applicant's Name and Address]{.underline}:** Centerpulse Spine-Tech
> Division (formerly Sulzer Spine-Tech)
>
> 7375 Bush Lake Road
>
> Minneapolis, Minnesota 55439
>
> **[Date of Panel Recommendation]{.underline}:** January 19, 2001
>
> **[Premarket Approval]{.underline}**
>
> **[(PMA) Application Number]{.underline}:** P980048
>
> **[Date of Notice of Approval]{.underline}:** April 20, 2001

## Indications for Use

The BAK/Cervical (hereinafter called the BAK/C) Interbody Fusion System
is indicated for use in skeletally mature patients with degenerative
disc disease (DDD) of the cervical spine with accompanying radicular
symptoms at one disc level. DDD is defined as discogenic pain with
degeneration of the disc confirmed by history and radiographic studies.
BAK/C implants are used to facilitate fusion in the cervical spine and
are placed via an anterior approach at the C‑3 to C‑7 disc levels using
autograft bone.

## Contraindications

> BAK/C devices should not be implanted in patients with:

-   an active infection

-   an allergy to titanium or titanium alloy

## Precautions

Surgeons should not implant the BAK/C Interbody Fusion System until
receiving adequate training regarding the surgical technique. Inadequate
training may result in poor patient outcomes and/or increased rates of
adverse events. See the BAK/C Interbody Fusion System Surgical Technique
Manual for more information on proper implantation technique.

No implant should be re-used if it has come in contact with human tissue
or bodily fluid.

## Device Description

The BAK/C Interbody Fusion System consists of implants and
instrumentation designed specifically for implantation of these devices.
The implants have the following design characteristics:

-   Implants are machined from rolled stock titanium alloy (Ti-6Al-4V,
    ASTM F136).

-   Each implant is a hollow, threaded cylinder. The leading thread of
    each device begins as a V-form thread and transitions to a flat
    modified square thread covering the entire outer surface of the
    implant. The threads have a pitch of 0.083". The device is conically
    tapered (28°) on its leading (posterior) edge. The trailing
    (anterior) edge has a threaded center hole with four pinholes
    designed to mate with the implant driver.

-   Its surface is perforated with 0.1094" diameter holes which are
    machined through the device wall at angles between 10° and 15° off
    the central axis. The number of holes varies by implant diameter:
    there are 12 on the 6mm implant; 18 on the 8mm, 24 on the 10mm, and
    30 on the 12mm.

-   During preparation of the disc space, local bone fragments are
    collected inside the reaming instrument and are placed into the
    BAK/C implant in order to minimize the need for harvesting
    additional bone from the iliac crest.

-   When implanted in pairs, the devices are placed 1mm apart from each
    other; when implanted singly, the implants are placed in the center
    of the disc space.

-   The following implant sizes (minor diameter x length) are available:

+-------------------------------+--------------------------------------+
| **part number**               | **description**                      |
+-------------------------------+--------------------------------------+
| > 6000-0612-00                | > 6 x 12mm implant                   |
+-------------------------------+--------------------------------------+
| > 6000-0812-00                | > 8 x 12mm implant                   |
+-------------------------------+--------------------------------------+
| > 6000-1012-00                | > 10 x 12mm implant                  |
+-------------------------------+--------------------------------------+
| > 6000-1212-00                | > 12 x 12mm implant                  |
+-------------------------------+--------------------------------------+

> Note: The 6 and 8mm devices generally are implanted in pairs; the 10
> and 12mm devices typically are implanted singly.

## Alternative Practices and Procedures

Alternative surgical treatments include, but are not limited to, various
bone grafting techniques (e.g., Cloward bone dowels, Smith Robinson
tri-cortical wedges, and Keystone grafts) used in conjunction with
anterior cervical discectomy with fusion (ACDF) procedures. These bone
grafting techniques are sometimes reinforced with cervical plating.

Non-operative alternative treatments include, but are not limited to,
medication including analgesics and muscle relaxants, heat, rest,
transcutaneous nerve stimulation (TENS), traction, hydrotherapy,
stretching and strengthening exercises, patient education, use of good
body mechanics, local injections, braces, and chiropractic care.

## Marketing History

The device has a marketing history in the following countries:
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czech
Republic, Denmark, Finland/Estonia, France, Germany, Greece, Hong Kong,
Iceland, Italy, Japan, Luxembourg, Netherlands, Norway, Philippines,
Poland, Portugal, Puerto Rico, Singapore, Slovenia, South Africa, Spain,
Sweden, Switzerland, Taiwan, Turkey, United Kingdom, and Venezuela. The
BAK/C has not been withdrawn from marketing for any reason relating to
the safety and effectiveness of the device.

## Adverse Effects of the Device on Health

A total of 164 BAK/C device patients and 134 anterior cervical
discectomy and fusion (ACDF) patients were enrolled in a multi-center
clinical study of the BAK/C Interbody Fusion System. In the BAK/C
patient group, the most common adverse event was degeneration of an
adjacent disc (6%). Other adverse events that occurred in at least 1% of
the study population include: continuing or new symptoms (1.9%),
degeneration of a non-adjacent disc (1.7%), dural tear (1.3%),
incision-related events (1.5%), pseudoarthrosis (1.5%), and vocal
paresis (1.2%). See Table 1 for a summary of adverse event rates
observed in the clinical study; events are listed in alphabetical order.
A complication reported at multiple time points is indicated as one
event and listed at the time of first report. The complication rates for
each follow-up interval were calculated by dividing the number of
patients experiencing a given complication by the total number of
patients with available data. The cumulative complication rates in Table
1 were derived using survival analysis techniques. The product of the
proportion of patients free from adverse events over each time interval
resulted in the cumulative rates provided in the table.

For the adverse events described in Table 1, some patients required
additional surgery to treat the complication. The most common of these
events was degeneration of an adjacent disc (2.8%). Other adverse events
requiring additional surgery in at least 1% of the study population
include: degeneration of a non-adjacent disc (1.7%), pseudoarthrosis
(1.5%). See Table 2 for a summary of the complications that led to
surgical interventions subsequent to the clinical trial surgery.

Surgical interventions subsequent to the clinical trial surgery can also
by stratified by the types of operations performed. These included
*revision, removal, supplemental fixation,* and *reoperation*. See Table
3 for a summary of the types of additional surgeries that were
conducted.

Table 1: Complications at Each Time Point (Unrestricted^1^ Cohort)

<table>
<colgroup>
<col style="width: 14%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 6%" />
</colgroup>
<tbody>
<tr class="odd">
<td></td>
<td colspan="2"><p><strong>Operative</strong></p>
<p><strong>Number (%)</strong></p></td>
<td colspan="2"><p>Post-op</p>
<p>(1 day to</p>
<p>1 ½ months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>3-month</p>
<p>(1 ½ months to</p>
<p>4 ½ months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>6-Month</p>
<p>( 4 ½ months to</p>
<p>9 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>12-Month</p>
<p>( 9 months to</p>
<p>18 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>24-Month</p>
<p>(greater than</p>
<p>18 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>Cumulative<sup>2</sup> Complication Rate % at</p>
<p>24-months</p></td>
</tr>
<tr class="even">
<td></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 164</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 134</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 154</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>N = 125</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 147</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>N = 118</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 116</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 86</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 126</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 94</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 101</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 80</strong></p></td>
<td><strong>BAK/C</strong></td>
<td><strong>Control</strong></td>
</tr>
<tr class="odd">
<td>Anesthesia-related</td>
<td>1 (0.6)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.6</td>
<td>-</td>
</tr>
<tr class="even">
<td>Continued/new symptoms</td>
<td>-</td>
<td>-</td>
<td>1 (0.6)</td>
<td>-</td>
<td>1 (0.7)</td>
<td>1 (0.8)</td>
<td>-</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1.9</td>
<td>0.8</td>
</tr>
<tr class="odd">
<td>Degeneration/adjacent disc</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>3 (2.6)</td>
<td>1 (1.2)</td>
<td>2 (1.6)</td>
<td>4 (4.3)</td>
<td>3 (3.0)</td>
<td>-</td>
<td>6.0</td>
<td>4.7</td>
</tr>
<tr class="even">
<td>Degeneration/non-adj. disc</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (1.0)</td>
<td>-</td>
<td>1.7</td>
<td>-</td>
</tr>
<tr class="odd">
<td>Dural tear</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.7)</td>
<td>-</td>
<td>1 (0.9)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1.3</td>
<td>-</td>
</tr>
<tr class="even">
<td>Dysphagia</td>
<td>-</td>
<td>1 (0.7)</td>
<td>1 (0.6)</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>2 (2.5)</td>
<td>0.6</td>
<td>4.5</td>
</tr>
<tr class="odd">
<td>Implant/Graft collapse</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>3 (2.4)</td>
<td>-</td>
<td>3 (2.5)</td>
<td>-</td>
<td>1 (1.2)</td>
<td>-</td>
<td>2 (2.1)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>6.3<sup>3</sup></td>
</tr>
<tr class="even">
<td>Graft migration</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.8</td>
</tr>
<tr class="odd">
<td>Incision related</td>
<td>-</td>
<td>2 (1.5)</td>
<td>1 (0.6)<sup>4</sup></td>
<td>7 (5.6) <sup>4</sup></td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (1.0)</td>
<td>-</td>
<td>1.5</td>
<td>6.9<sup>5</sup></td>
</tr>
<tr class="even">
<td>Increased instability</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (1.2)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.8</td>
</tr>
<tr class="odd">
<td>Myocardial infarction</td>
<td>1 (0.6)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.6</td>
<td>-</td>
</tr>
<tr class="even">
<td>Pneumonia</td>
<td>-</td>
<td>-</td>
<td>1 (0.6)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.6</td>
<td>-</td>
</tr>
<tr class="odd">
<td>Pseudoarthrosis</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>3 (2.5)</td>
<td>1 (0.9)</td>
<td>2 (2.3)</td>
<td>1 (0.8)</td>
<td>1 (1.1)</td>
<td>1 (1.0)</td>
<td>-</td>
<td>1.5</td>
<td>4.9</td>
</tr>
<tr class="even">
<td>Spinal stenosis</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.7)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.6</td>
<td>-</td>
</tr>
<tr class="odd">
<td>Thrombophlebitis</td>
<td>-</td>
<td>-</td>
<td>1 (0.6)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.6</td>
<td>-</td>
</tr>
<tr class="even">
<td>Vocal paresis</td>
<td>1 (0.6)</td>
<td>-</td>
<td>1 (0.6)</td>
<td>1 (0.8)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1.2</td>
<td>0.8</td>
</tr>
<tr class="odd">
<td>Other</td>
<td>-</td>
<td>1 (0.7)<sup>6</sup></td>
<td>1 (0.6)<sup>7</sup></td>
<td>1 (0.8)<sup>8</sup></td>
<td>1 (0.7)<sup>9</sup></td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (1.0)<sup>10</sup></td>
<td></td>
<td>2.1</td>
<td>1.5</td>
</tr>
<tr class="even">
<td><strong>Total</strong></td>
<td>3 (1.8)</td>
<td>4 (3.0)</td>
<td>7 (4.5)<sup>11</sup></td>
<td>14 (11.2) <sup>11</sup></td>
<td>4 (2.7)</td>
<td>8 (6.8)</td>
<td>5 (4.3)</td>
<td>5 (5.8)</td>
<td>5 (4.0)</td>
<td>7 (7.4)</td>
<td>7 (6.9)</td>
<td>2 (2.5)</td>
<td>16.9</td>
<td>25.3<sup>12</sup></td>
</tr>
</tbody>
</table>

^1^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
Restricted and Unrestricted Cohorts

^2^ Based on Life Table analysis

^3^ Overall cumulative difference statistically significant at 0.0014
using Wilcoxon (Gehan) statistical test

^4^ Difference statistically significant at 0.024 using Fishers exact
test

^5^Overall cumulative difference statistically significant at 0.0142
using Wilcoxon (Gehan) statistical test

^6^Laryngeal spasm: During extubation, patient developed laryngospasm
that was treated with Lasix

^7^Paraspinous spasm: 3 days post-operatively, patient complained of
pain and spasm which was treated with intravenous muscle relaxant

^8^Hematoma: 3 days post-operatively, patient complained of swelling in
neck without signs of infection that was treated with 1 day course of
Decadron and observation

^9^Nerve root compression: Patient reported arm pain. CT revealed
adjacent level nerve root compression resulting from disc herniation;
symptoms did not correlate with adjacent level disease

^10^Injury: Complained of increased cervical pain following involvement
in altercation

^11^Difference statistically significant at 0.042 using Fishers exact
test

^12^Overall cumulative difference statistically significant at 0.0178
using Wilcoxon (Gehan) statistical test

**Table 2: Complications Requiring Additional Surgery (Unrestricted^1^**
Cohort)

<table>
<colgroup>
<col style="width: 17%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
</colgroup>
<tbody>
<tr class="odd">
<td></td>
<td colspan="2"><p>Post-op</p>
<p>(1 day to</p>
<p>1 ½ Months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>3-month</p>
<p>(1 ½ months to</p>
<p>4 ½ Months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>6-Month</p>
<p>(4 ½ months to</p>
<p>9 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>12-Month</p>
<p>(9 months to</p>
<p>18 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>24-Month</p>
<p>(greater than</p>
<p>18 Months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>Cumulative<sup>2</sup> Complication Rate % at</p>
<p>24-months</p></td>
</tr>
<tr class="even">
<td></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 154</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>N = 125</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 147</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>N = 118</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 116</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 86</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 126</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 94</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 101</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 80</strong></p></td>
<td><strong>BAK/C</strong></td>
<td><strong>Control</strong></td>
</tr>
<tr class="odd">
<td>Continued/new symptoms</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.8)</td>
<td>1 (1.1)</td>
<td>-</td>
<td>-</td>
<td>0.68</td>
<td>0.77</td>
</tr>
<tr class="even">
<td>Degeneration adj. disc</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.9</td>
<td>1 (1.2)</td>
<td>3 (2.4)<sup>3</sup></td>
<td>3 (3.2)<sup>4</sup></td>
<td>-</td>
<td>-</td>
<td>2.79</td>
<td>3.72</td>
</tr>
<tr class="odd">
<td>Degeneration non-adj. disc</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.8)<sup>3</sup></td>
<td>1 (1.1)</td>
<td>2 (2.0)</td>
<td>-</td>
<td>1.71</td>
<td>-</td>
</tr>
<tr class="even">
<td>Implant/Graft collapse</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (1.2)</td>
<td>-</td>
<td>2 (2.1)<sup>4</sup></td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>3.89<sup>5</sup></td>
</tr>
<tr class="odd">
<td>Pseudoarthrosis</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.9)</td>
<td>1 (1.2)</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (1.0)</td>
<td>2 (2.5)</td>
<td>1.50</td>
<td>2.38</td>
</tr>
<tr class="even">
<td>Spinal stenosis</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.9)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.62</td>
<td>-</td>
</tr>
<tr class="odd">
<td>Nerve root compression</td>
<td>-</td>
<td>-</td>
<td>1 (0.7)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.62</td>
<td>-</td>
</tr>
<tr class="even">
<td><strong>Total</strong></td>
<td>-</td>
<td>1 (0.8)</td>
<td>1 (0.7)</td>
<td>1 (0.8)</td>
<td>3 (2.6)</td>
<td>3 (3.5)</td>
<td>6 (4.8)</td>
<td>7 (7.4)</td>
<td>3 (3.0)</td>
<td>2 (2.5)</td>
<td>6.22</td>
<td>10.78</td>
</tr>
</tbody>
</table>

^1^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
Restricted and Unrestricted Cohorts

^2^ Based on Life Table Analysis

^3^ A single patient experienced 2 separate events (9 months
post-operative: adjacent level DDD; 16 months post-operative: disc
herniation at a non-adjacent level)

^4^ A single patient experienced 2 separate events (10 months
post-operative: graft collapse revised with plate and allograft; 13
months post-operative: graft collapse with hardware failure treated with
fibular strut, plating and halo application

^5^ Cumulative difference statistically significant at 0.0121 using
Wilcoxon (Gehan) statistical test

Table 3: Additional Surgery Categories (Unrestricted^1^ Cohort)

<table>
<colgroup>
<col style="width: 17%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 7%" />
</colgroup>
<tbody>
<tr class="odd">
<td></td>
<td colspan="2"><p>Post-op</p>
<p>(1 day to</p>
<p>1 ½ Months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>3-month</p>
<p>(1 ½ months to</p>
<p>4 ½ Months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>6-Month</p>
<p>(4 ½ months to</p>
<p>9 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>12-Month</p>
<p>(9 months to</p>
<p>18 months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>24-Month</p>
<p>(greater than</p>
<p>18 Months)</p>
<p>Number (%)</p></td>
<td colspan="2"><p>Cumulative<sup>2</sup> Complication Rate % at</p>
<p>24-months</p></td>
</tr>
<tr class="even">
<td></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 154</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>N = 125</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 147</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>N = 118</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 116</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 86</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 126</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 94</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>n = 101</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>n = 80</strong></p></td>
<td><strong>BAK/C</strong></td>
<td><strong>Control</strong></td>
</tr>
<tr class="odd">
<td>Revisions<sup>3</sup></td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (1.2)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.0</td>
<td>0.8</td>
</tr>
<tr class="even">
<td>Removals<sup>4</sup></td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>1 (0.9)</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>-</td>
<td>0.6</td>
<td>0.0</td>
</tr>
<tr class="odd">
<td>Supplemental Fixation<sup>5</sup></td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (0.8)</td>
<td>-</td>
<td>1 (1.2)</td>
<td>3 (2.4)</td>
<td>3 (3.2)</td>
<td>1 (1.0)</td>
<td>2 (2.5)</td>
<td>4.3</td>
<td>4.6</td>
</tr>
<tr class="even">
<td>Reoperations<sup>6</sup></td>
<td>-</td>
<td>-</td>
<td>1 (0.7)</td>
<td>-</td>
<td>2 (1.7)</td>
<td>1 (1.2)</td>
<td>2 (1.6)</td>
<td>4 (4.3)</td>
<td>2 (2.0)</td>
<td>-</td>
<td>2.9</td>
<td>8.8</td>
</tr>
<tr class="odd">
<td><strong>Total</strong></td>
<td>-</td>
<td>1 (0.8)</td>
<td>1 (0.7)</td>
<td>1 (0.8)</td>
<td>3 (2.6)</td>
<td>3 (3.5)</td>
<td>5 (4.0)<sup>7</sup></td>
<td>7 (7.4)</td>
<td>3 (3.0)</td>
<td>2 (2.5)</td>
<td>6.22</td>
<td>10.78</td>
</tr>
</tbody>
</table>

^1^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
Restricted and Unrestricted Cohorts

^2^ Based on Life Table Analysis

^3^ Revision = An operation that adjusts the implant configuration

^4^ Removal = an operation that removes the implant is removed with or
without replacing it

^5^ Supplemental Fixation = an operation that implants an additional
spinal device(s)

^6^ Reoperation = an operation that does *not* remove, modify or add any
implant components

^7^ Total differs from Table 2 because a single patient had [1
Supplemental Fixation]{.underline} procedure to correct [2
complications]{.underline} (i.e., 1 report of pseudoarthrosis and 1
report of non-adjacent disc degeneration)

## Potential Adverse Effects of the Device on Health:

The following is a list of potential adverse events which may occur with
cervical interbody fusion surgery with the BAK/C Interbody Fusion
System. Some of these events may have been reported previously in the
adverse events tables.

-   Disassembly, bending, breakage, loosening, and/or migration of
    components.

-   Foreign body (allergic) reaction.

-   Tissue or nerve damage.

-   Post-operative change in spinal curvature, loss of correction,
    height, and/or reduction.

-   Infection.

-   Dural tears.

-   Neurological system compromise.

-   Dysphagia/dysphonia

-   Scar formation.

-   Bone fracture.

-   Non-union (or pseudarthrosis), delayed union, mal-union.

-   Cessation of any potential growth of the operated portion of the
    spine. Loss of spinal mobility or function.

-   Graft donor site complications.

-   Damage to blood vessels and cardiovascular system compromise.

-   Gastrointestinal complications.

-   Damage to internal organs and connective tissue.

-   Development of respiratory problems.

-   Incisional complications.

-   Change in mental status.

-   Death.

> **Note:** Additional surgery may be necessary to address some of these
> potential adverse events.

## Pre-Clinical Studies

This section provides summaries of preclinical tests performed on the
BAK/C Interbody Fusion System. Table 4 describes the non-clinical
studies and is divided into the following categories: Bench Testing and
Animal Testing.

Finite Element Analysis (FEA) was conducted on all sizes of the BAK/C
implant. From the FEA, Sulzer Spine-Tech determined that the 6mm implant
represents the worst case construct. Therefore, 6mm implants were used
to determine the ultimate strength of the device.

> Table 4: Summary of Pre-Clinical Studies

+----------------------------------+-----------------------------------+
| Study                            | Results/Conclusions               |
+----------------------------------+-----------------------------------+
| ***Bench Testing***              |                                   |
+----------------------------------+-----------------------------------+
| **Ultimate Static Strength**,    | 4929.16 ± 563.1N                  |
| 6mm implant                      |                                   |
|                                  | Therefore, the device should      |
| (ASTM draft F-04.25.02.02)       | withstand anticipated loads in    |
|                                  | the cervical spine.               |
|                                  |                                   |
|                                  | NOTE: SST estimated the axial     |
|                                  | compressive load in the cervical  |
|                                  | spine based upon *in vivo*        |
|                                  | intradiscal pressures published   |
|                                  | in the literature by Hattori      |
|                                  | (1981). From Hattori's research , |
|                                  | SST estimated the cervical        |
|                                  | intervertebral load to be 118.8   |
|                                  | N. SST established a clinical     |
|                                  | load requirement of 356 N         |
|                                  | (80 lbs) by assuming a safety     |
|                                  | factor of three (i.e., 118.8 x 3  |
|                                  | = 356.4)                          |
+----------------------------------+-----------------------------------+
| **Dynamic Compression Strength** | Implant survived 5 million cycles |
|                                  | at 533.8 N.                       |
| (ASTM draft F-04.25.02.02)       |                                   |
|                                  | Therefore, the device should      |
|                                  | withstand anticipated loads in    |
|                                  | the cervical spine. See Note      |
|                                  | above.                            |
+----------------------------------+-----------------------------------+
| ***In Vitro* Flexibility and     | No statistically significant      |
| Stability**                      | differences in range of motion,   |
|                                  | neutral zone, or average          |
| Testing was conducted on human   | stiffness were found between      |
| cadaveric spines to determine    | construct groups (i.e., single    |
| any differences in spine         | vs. paired implants) with one     |
| stability due to the number of   | exception -- change in neutral    |
| implants placed at a spinal      | zone for axial rotation.          |
| level (i.e., one vs. two).       |                                   |
| Single and paired BAK/C implants | Therefore, there are no relevant  |
| were placed at C4-C5 and C6-C7   | differences in initial stability  |
| in 13 spines as follows:         | between the single or paired      |
|                                  | configurations of the BAK/C       |
| -   6 single BAK/C implants at   | implant.                          |
|     C4-C5                        |                                   |
|                                  |                                   |
| -   5 paired BAK/C implants at   |                                   |
|     C4-C5                        |                                   |
|                                  |                                   |
| -   6 single BAK/C implants at   |                                   |
|     C6-C7                        |                                   |
|                                  |                                   |
| -   5 paired BAK/C implants at   |                                   |
|     C6-C7                        |                                   |
+----------------------------------+-----------------------------------+
| ***Animal Testing***             |                                   |
+----------------------------------+-----------------------------------+
| **Goat Cervical Spine Model**    | No statistical differences were   |
|                                  | seen in the stability data.       |
| Three adjacent levels (C3-C6)    | Fusion was observed as follows:   |
| were instrumented with one of    |                                   |
| the following:                   | -   48% of the levels implanted   |
|                                  |     with the uncoated BAK/C were  |
| -   uncoated BAK/C with          |     fused                         |
|     autograft (n=7 animals, 21   |                                   |
|     levels)                      | -   62% of the spinal levels      |
|                                  |     implanted with the HA‑coated  |
| -   HA-coated BAK/C with         |     BAK/C were fused              |
|     autograft (n=7 animals, 21   |                                   |
|     levels)                      |                                   |
|                                  |                                   |
| Radiographs were taken at 1, 3,  |                                   |
| 6, 9, and 12 weeks. The animals  |                                   |
| were sacrificed at 12 weeks. The |                                   |
| harvested spines were subjected  |                                   |
| to stability testing followed by |                                   |
| histological analysis. Sagittal  |                                   |
| micro-radiographs were used to   |                                   |
| assess fusion.                   |                                   |
+----------------------------------+-----------------------------------+
| **Sheep Cervical Fusion Model**  | Fusion rates were:                |
|                                  |                                   |
| This study compared the          | -   33% for the BAK/C group       |
| following three constructs:      |                                   |
|                                  | -   67% for the autograft bone    |
| -   BAK/C implant filled with    |     group                         |
|     autograft (n=3 animals, 6    |                                   |
|     levels)                      | -   100% for the anterior plate   |
|                                  |     group                         |
| -   uninstrumented autograft     |                                   |
|     iliac crest grafts (n=3      |                                   |
|     animals, 6 levels)           |                                   |
|                                  |                                   |
| -   autograft iliac crest grafts |                                   |
|     with anterior plating (n=3   |                                   |
|     animals, 6 levels)           |                                   |
|                                  |                                   |
| Radiographs were used to assess  |                                   |
| fusion.                          |                                   |
+----------------------------------+-----------------------------------+

## Summary of Clinical Study

### Study Design

The clinical study for the BAK/C Interbody Fusion System compared BAK/C
implants to an [anterior cervical discectomy and fusion]{.underline}
(ACDF) surgical procedure for the treatment of cervical degenerative
disc disease. The study was designed as an equivalence trial to evaluate
the safety and effectiveness of the device in a prospective, randomized,
multi-center, controlled investigation. The effectiveness measures
selected for this investigation evaluated whether the affected disc
level was fused, whether there was relief from neck pain and radicular
symptoms (arm/shoulder pain, loss of muscle strength, sensation
abnormalities) and whether there were improvements in patient function
(physical and mental). Safety information was measured by an analysis of
adverse event reports.

### Inclusion/Exclusion Criteria

Patients were enrolled in this study according to the following
inclusion/exclusion criteria:

*[Inclusion criteria]{.underline}*

-   Discogenic radiculopathy of the cervical spine at levels between C-3
    and C-7

-   Radicular symptoms (arm-shoulder pain, decreased strength, abnormal
    sensation, and/or abnormal reflexes)

-   Discogenic origin of disease confirmed by radiographic analysis,
    including one or more of the following:

-   degenerated (darkened) disc on MRI

-   decreased disc height compared to adjacent normal discs on x-ray, CT
    or MRI,

-   disc herniation on CT or MRI

-   Age between 18 and 65 years old

*[Exclusion criteria]{.underline}*

-   Systemic infections

-   Significant metabolic bone disease (i.e., osteoporosis or
    osteomalacia)

-   Circulatory, cardiac or pulmonary problems

-   Active malignancy

-   Non-discogenic cause of symptoms (e.g., cervical tumor)

-   Degenerative disc disease of three or more cervical spine segments

-   Previous fusion attempt at same level

-   Acute cervical trauma and/or significant instability (i.e.,
    subluxation \>3mm on lateral flexion/extension x-rays)

-   Rheumatoid disease of the cervical spine

-   Moderate to severe myelopathy

### Demographic Data

Two hundred ninety-eight (298) patients (164-BAK/C patients; 134-ACDF
patients) were enrolled at 28 institutions in the United States. Of the
patients enrolled, 48.7% were female and 51.3% were male; the mean age
at enrollment was 44.1 years. A total of 45.1% patients experienced
symptoms of cervical degenerative disc disease with radicular
involvement for more than nine months prior to enrollment in the study;
34% had experienced symptoms for between 3 and 9 months; and 20.1% had
experienced symptoms for less than 3 months. Compensation-related
injuries accounted for 29.5% of the study population. The study cohort
was comprised of patients employed preoperatively (53.4%), patients
unemployed and on disability (32.2%) and patients unemployed for other
reasons (14.4%). A total of 40.2% of the study population were smokers
preoperatively. There were no statistically significant demographic
differences identified between the BAK/C and ACDF patients.

### Treatment Protocol

Patients were randomized prior to surgery to the treatment (BAK/C
device) or control (anterior cervical discectomy with fusion, ACDF) arm
of the study. BAK/C patients received one or two devices at each spinal
level intended to be fused. Autograft and/or allograft were placed into
the BAK/C device(s) as part of the implant procedure to facilitate
fusion. Patient follow-up examinations were performed post-operatively,
and at 3, 6, 12, and 24 months after treatment. Follow-up examinations
were conducted annually after the 24-month time point.

*Outcomes Assessed and Success Criteria*

-   [Fusion]{.underline} was assessed by independent review of lateral
    flexion/extension (F/E) and anterior/posterior (A/P) radiographs.
    [Fusion success]{.underline} was defined as less than 4° of
    segmental movement on lateral flexion/extension x-rays with less
    than 2mm of radiolucent lines covering less than 50% of the
    implant's outer surface as visualized on AP and lateral x-rays.

-   [Neck pain]{.underline} status was determined by patient completion
    of a ten-point visual analog scale. [Neck pain success]{.underline}
    was defined as at least a 2-point improvement in neck pain score in
    patients with a preoperative score of 4 or more, or maintenance of
    the preoperative score in patients with preoperative scores of 3 or
    less**.**

-   [Radicular signs and symptoms]{.underline} measured included
    arm-shoulder pain, muscle strength, and sensation status.

-   [Arm-shoulder pain]{.underline} status was determined by patient
    completion of a ten-point visual analog scale. [Arm-shoulder pain
    success]{.underline} was defined as at least a 2-point improvement
    in arm-shoulder pain scores in patients with preoperative
    arm-shoulder pain scores of 4 or more, or maintenance of the
    preoperative score in patients with preoperative scores of 3 or
    less. Both limbs must have met the respective success criterion.

-   [Muscle strength]{.underline} status was determined by clinical
    assessment of the deltoid, biceps, and triceps muscles. [Muscle
    strength success]{.underline} was defined as maintenance of or
    improvement in muscle strength for the deltoids, biceps, and triceps
    in both arms. Patients presenting with preoperative muscle weakness
    with pre-op neck and arm-shoulder pain scores of 3 or less must have
    experienced improvement in the affected muscle group.

-   [Sensation]{.underline} status was determined by clinical
    assessment. [Sensation success]{.underline} was defined as
    maintenance of or improvement in sensation response in both arms.
    Patients presenting with pre-op neck and arm-shoulder pain scores of
    3 or less must have experienced an improvement in all preoperative
    sensory abnormalities.

-   [Function]{.underline} assessment consisted of Physical Component
    Summary Scales (PCS) and Mental Component Summary Scales (MCS)
    computed from patient responses to the SF-36 Health Survey.
    [Function success]{.underline} was defined as maintenance of or
    improvement in both the Physical Component Summary Scales (PCS) and
    Mental Component Summary Scales (MCS) according to the algorithm in
    the SF-36 user's manual.

-   [Overall success]{.underline} was defined as successful outcomes for
    each of the four previously described study outcomes (fusion, neck
    pain, radicular signs and symptoms, and function) without the
    necessity for additional surgery for supplemental fixation,
    revision, replacement, or removal of BAK/C system or bone graft
    implant.

-   [Safety]{.underline} was assessed by completing adverse event
    reports for all reported complications, including complications
    requiring additional surgery, implant-related complications, and
    complications related to the surgical procedure. [Safety
    success]{.underline} was defined as a complication rate for BAK/C
    that was *equivalent to* (i.e., no worse than) the complication rate
    experienced in patients receiving the ACDF procedure.

### Analysis Cohorts

Two patient cohorts were identified for analysis. [The first analysis
cohort was a subset of the second]{.underline}, and was made up of all
data available for patients that were due for follow-up as of November
1999, referred to as the "Restricted Cohort". The second analysis cohort
was made up of all data available for patients due for follow-up as of
June 20, 2000, referred to as the "Unrestricted Cohort". The proportion
of patients with [complete efficacy data]{.underline} in the Restricted
Cohort was greater than that of the Unrestricted Cohort, thus, efficacy
conclusions for the study are based on the results from the Restricted
Cohort. In contrast to efficacy data, the proportions of patients with
[complete safety data]{.underline} collected from the Restricted and
Unrestricted cohorts were comparable. In order to include all available
safety data, safety conclusions for the study are based on the results
from the Unrestricted Cohort.

Complete data from 18.7% of the Restricted Cohort was not available at
the time of data analysis. To investigate the possible effect of missing
data on the study conclusions, an additional analysis was conducted.
This "sensitivity analysis" examined a hypothetical scenario in which
missing data for ACDF patients showed better clinical results than
actual ACDF data collected. The results of this analysis showed that all
but one of the outcome measures were *not sensitive* to this
hypothetical advantage. Only the neck pain success measure was sensitive
to this hypothetical advantage.

### Patient Accountability

As stated previously, patient follow-up examinations were performed
immediately post-operatively, and at 3, 6, 12, and 24 months after
treatment. For patients missing their 24‑month evaluation, follow-up
data were attempted to be collected at time points greater than 24
months. Any data collected after the 24-month follow-up interval were
designated "24‑month **+**" data. The "24-month" and "24-month **+**"
evaluations were grouped and reported in the tables below as "Long-term"
results.

Of the 164 BAK/C patients and 134 ACDF patients enrolled, complete
safety and effectiveness data were not available for all patients at
each follow-up examination. **Table 5** provides a summary of the number
of patients who contributed complete safety data at each follow-up
interval. Safety data were considered complete if the patient had a
completed complication case report form and clinical assessments of
fusion and neck pain. The safety analyses were performed on the cohort
of all patients enrolled as of June 20, 2000. The denominator for each
interval represents the number of patients due for that follow-up
evaluation as of June 20, 2000. **Table 6** provides a summary of the
number of patients who contributed complete effectiveness data at 6 and
12 months and at 24 months or later. (*Note: The study protocol did not
require that complete effectiveness data be collected until the 6-month
examination).* Effectiveness data were considered complete if the
patient had clinical assessments of fusion, neck pain, radicular
symptoms, and function. The effectiveness analyses were performed on the
cohort of all patients due for follow-up as of November 17, 1999. The
denominator for each interval represents the number of patients due for
that follow-up evaluation as of November 17, 1999.

Table 5: Safety Data Accountability

<table style="width:100%;">
<colgroup>
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="2"><strong>Post-operative</strong></td>
<td colspan="2"><strong>3-month</strong></td>
<td colspan="2"><strong>6-month</strong></td>
<td colspan="2"><strong>12-month</strong></td>
<td colspan="2"><strong>Long-term<sup>1</sup></strong></td>
</tr>
<tr class="even">
<td><p><strong>BAK/C</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>BAK/C</strong></p>
<p><strong>x/n (%)</strong></p></td>
<td><p><strong>Control</strong></p>
<p><strong>x/n (%)</strong></p></td>
</tr>
<tr class="odd">
<td>154/164 (93.9)</td>
<td>125/134 (93.3)</td>
<td>147/164 (89.6)</td>
<td>118/134 (88.1)</td>
<td>116/164 (70.7)</td>
<td>86/134 (64.2)</td>
<td>126/161 (78.3)</td>
<td>94/131 (71.8)</td>
<td>101/144 (70.1)</td>
<td>80/118 (67.8)</td>
</tr>
</tbody>
</table>

^1^ Follow-up examination conducted 24 months post-operatively or later

Table 6: Effectiveness Data Accountability

+-----------+-----------+-----------+-----------+-----------+-----------+
| **        |           | **1       |           | **Long-   |           |
| 6-month** |           | 2-month** |           | term^1^** |           |
+-----------+-----------+-----------+-----------+-----------+-----------+
| **BAK/C** | **        | **BAK/C** | **        | **BAK/C** | **        |
|           | Control** |           | Control** |           | Control** |
| **x/n     |           | **x/n     |           | **x/n     |           |
| (%)**     | **x/n     | (%)**     | **x/n     | (%)**     | **x/n     |
|           | (%)**     |           | (%)**     |           | (%)**     |
+-----------+-----------+-----------+-----------+-----------+-----------+
| 114/160   | 85/130    | 124/150   | 94/122    | 85/101    | 66/87     |
|           |           |           |           |           |           |
| (71.3)    | (65.4)    | (82.7)    | (77.0)    | (84.2)    | (75.9)    |
+-----------+-----------+-----------+-----------+-----------+-----------+

^1^ Follow-up examination conducted 24 months post-operatively or later

### Statistical Analysis 

Safety and efficacy of the BAK/C implants were assessed through Bayesian
statistical methods; however, classical statistical analyses were
conducted to aid in the interpretation of the study results. The
Bayesian approach is a method that can be used to directly address the
question of equivalence. Study conclusions regarding both efficacy
(outcome measures) and safety (adverse events) were made based on the
pre-determined definition of equivalence, specifically, a log-odds
advantage of [-0.811]{.underline}. Thus, a 90% credible interval that is
completely above [+0.811]{.underline} corresponds to a conclusion of
superiority; a 90% credible interval that is completely above
[-0.811]{.underline} corresponds to a conclusion of equivalence, and a
90% credible interval that contains [-0.811]{.underline} corresponds to
a conclusion of no strong evidence for equivalence.

### Effectiveness Analyses

The Bayesian analysis methods employed to assess safety and
effectiveness combine data with a diffuse prior distribution to
determine the posterior distribution of the parameters of interest. The
posterior distributions of the parameter, in conjunction with certain
contrasts of interest, form the basis for determination of success
outcomes. The posterior distribution can be summarized by 95% credible
intervals. The lower and upper limits of this interval are such that 95%
of the posterior distribution is contained between the lower and upper
limits of this interval, 2.5% below the lower limit and 2.5% above the
upper limit. The Bayesian analysis results presented in the following
section provide the Bayesian [study effectiveness results]{.underline}
based on the patient population referenced in Table 6**.** The lower and
upper limits of the posterior distributions of the difference in BAK/C
and ACDF success rates are summarized for each of the success measures.

*NOTE: The BAK/C clinical study included patients who received treatment
at two adjacent levels. Data were collected from fifty-one (51)
two-level BAK/C patients and twenty-eight (28) two-level ACDF patients.
Results of the statistical analysis performed on two-level patients were
inconclusive and therefore safety and effectiveness for two‑level
patients were not established. The BAK/C Interbody Fusion System is not
indicated for patients affected with cervical degenerative disc disease
at more than one level. **The results summarized below pertain to
one-level patients only.***

#### Fusion

> [Fusion: Bayesian Analysis Results]{.underline}
>
> Table 7 provides the Bayesian [fusion success results]{.underline}
> based on the patient population referenced in Table 6**.** The lower
> and upper limits of the posterior distributions of the difference in
> BAK/C and ACDF success rates are summarized.
>
> Table 7: Long-term^1^ Fusion -- Bayesian Analysis Results
> (Restricted^2^ Cohort)

+-----------------------+-----------------------+-----------------------+
| Success Measure       | 95% Credible Interval | Multivariate          |
|                       | for Difference in     | Longitudinal          |
|                       | BAK/C and ACDF        |                       |
|                       | Rates^3^              | Bayesian Analysis     |
|                       |                       | Conclusion            |
+-----------------------+-----------------------+-----------------------+
| Fusion                | (+3.2, +6.1)          | BAK/C is superior to  |
|                       |                       | ACDF                  |
+-----------------------+-----------------------+-----------------------+

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts
>
> ^3^ Predictive distributions calculated from Long-Term multivariate
> longitudinal Bayesian results
>
> [Fusion: Classical Analysis Results]{.underline}
>
> Table 8 presents fusion success rates for patients over time. The
> analysis showed a statistically significant difference in fusion rates
> between the study groups at the 6-month, 12-month, and long-term
> follow-up, attributable to lower rates of fusion in the Control group.
>
> Table 8: Long-term^1^ Fusion - Classical Analyses Results
> (Restricted^2^ Cohort)

  ----------- ----------- ----------- ----------- ----------- ------------
              BAK/C                   Control                 

              x/n         \%          x/n         \%          P

  6 month     119/120     99.2        77/94       81.9        \<0.001

  12 month    123/126     97.6        86/97       88.7        0.010

  Long-Term   86/86       100.0       66/69       95.7        0.086
  ----------- ----------- ----------- ----------- ----------- ------------

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts

#### Neck Pain

> [Neck Pain: Bayesian Analysis Results]{.underline}
>
> Table 9 provides the Bayesian [neck pain success results]{.underline}
> based on the patient population referenced in Table 6**.** The lower
> and upper limits of the posterior distributions of the difference in
> BAK/C and ACDF success rates are summarized.
>
> Table 9: Long-Term^1^ Neck Pain -- Bayesian Analysis Results
> (Restricted^2^ Cohort)

+-----------------+-----------------------+----------------------------+
| Success Measure | 95% Credible Interval | Multivariate Longitudinal  |
|                 | for Difference in     |                            |
|                 | BAK/C and ACDF        | Bayesian Analysis          |
|                 | Rates^3^              | Conclusion                 |
+-----------------+-----------------------+----------------------------+
| Neck Pain       | (-5.6, +3.7)          | Satisfies criterion for    |
|                 |                       | equivalence                |
+-----------------+-----------------------+----------------------------+

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts
>
> ^3^ Predictive distributions calculated from Long-Term multivariate
> longitudinal Bayesian results
>
> [Neck Pain: Classical Analysis Results]{.underline}
>
> Table 10 presents the neck pain success rates for study group at 6,
> 12, and long-term. No statistical differences in neck pain success
> were found between the study groups.
>
> Table 10: Long-Term^1^ Neck Pain -Classical Analysis Results
> (Restricted^2^ Cohort)

  ----------- ----------- ----------- ----------- ----------- -------------
              BAK/C                   Control                 

              x/n         \%          x/n         \%          p

  6 month     108/135     80.0        76/103      73.8        Not
                                                              significant

  12 month    108/138     78.3        83/100      83.0        Not
                                                              significant

  Long-Term   76/90       84.4        59/71       83.1        Not
                                                              significant
  ----------- ----------- ----------- ----------- ----------- -------------

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts

#### Overall Radicular

> [Overall Radicular: Bayesian Analysis Results]{.underline}
>
> Table 11 provides the Bayesian [radicular success results]{.underline}
> based on the patient population referenced in Table 6**.** The lower
> and upper limits of the posterior distributions of the difference in
> BAK/C and ACDF success rates are summarized.
>
> **Table 11: Long-Term^1^ Radicular -- Bayesian Analysis Results
> (Restricted^2^** Cohort)

+-------------------+-----------------------+--------------------------+
| Success Measure   | 95% Credible Interval | Multivariate             |
|                   | for Difference in     | Longitudinal             |
|                   | BAK/C and ACDF        |                          |
|                   | Rates^3^              | Bayesian Analysis        |
|                   |                       | Conclusion               |
+-------------------+-----------------------+--------------------------+
| Radicular         | (-0.7, +9.3)          | Satisfies criterion for  |
|                   |                       | equivalence              |
+-------------------+-----------------------+--------------------------+

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts
>
> ^3^ Predictive distributions calculated from Long-Term multivariate
> longitudinal Bayesian results
>
> [Overall Radicular: Classical Analysis Results]{.underline}
>
> Table 12 presents a summary of overall radicular success rates by
> study group across time. No statistical differences were found between
> study groups.
>
> Table 12: Long-Term^1^ Radicular--Classical Analysis Results
> (Restricted^2^ Cohort)

  ----------- ----------- ----------- ----------- ----------- -------------
              BAK/C                   Control                 

              x/n         \%          x/n         \%          p

  6 month     99/160      61.9        66/130      50.8        Not
                                                              significant

  12 month    104/137     75.9        74/100      74.0        Not
                                                              significant

  Long-Term   72/90       80.0        54/71       76.1        Not
                                                              significant
  ----------- ----------- ----------- ----------- ----------- -------------

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts

#### Function

> [Function: Bayesian Analysis Results]{.underline}
>
> Table 13 provides the Bayesian [function success results]{.underline}
> based on the patient population referenced in Table 6**.** The lower
> and upper limits of the posterior distributions of the difference in
> BAK/C and ACDF success rates are summarized.
>
> Table 13: Long-Term^1^ Function-Bayesian Analysis Results
> (Restricted^2^ Cohort)

+-------------------+-----------------------+--------------------------+
| Success Measure   | 95% Credible Interval | Multivariate             |
|                   | for Difference in     | Longitudinal             |
|                   | BAK/C and ACDF        |                          |
|                   | Rates^3^              | Bayesian Analysis        |
|                   |                       | Conclusion               |
+-------------------+-----------------------+--------------------------+
| Function          | (-2.1, +7.1)          | Satisfies criterion for  |
|                   |                       | equivalence              |
+-------------------+-----------------------+--------------------------+

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts
>
> ^3^ Predictive distributions calculated from Long-Term multivariate
> longitudinal Bayesian results
>
> [Function: Classical Analyses Results]{.underline}
>
> Table 14 presents a summary of function success rates by study group
> across time. No statistical differences were observed between study
> groups.
>
> Table 14: Long-Term^1^ Function Classical Analyses Results
> (Restricted^2^ Cohort)

  ----------- ----------- ----------- ----------- ----------- -------------
              BAK/C                   Control                 

              x/n         \%          x/n         \%          p

  6 month     107/131     81.7        74/95       77.9        Not
                                                              significant

  12 month    101/136     74.3        80/100      80.0        Not
                                                              significant

  Long-Term   70/89       78.7        51/68       75.0        Not
                                                              significant
  ----------- ----------- ----------- ----------- ----------- -------------

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts

#### Overall Success

> [Overall Success: Bayesian Analysis Results]{.underline}
>
> Table 15 provides the Bayesian [overall success results]{.underline}
> based on the patient population referenced in Table 6**.** The lower
> and upper limits of the posterior distributions of the difference in
> BAK/C and ACDF success rates are summarized.
>
> Table 15: Long-Term^1^ Overall Success-Bayesian Analysis Results
> (Restricted^2^ Cohort)

+----------------+-----------------------+-----------------------------+
| Success        | 95% Credible Interval | Multivariate Longitudinal   |
| Measure        | for Difference in     |                             |
|                | BAK/C and ACDF        | Bayesian Analysis           |
|                | Rates^3^              | Conclusion                  |
+----------------+-----------------------+-----------------------------+
| Overall        | (+9.9, +19.0)         | Satisfies criterion for     |
| Success        |                       | equivalence                 |
+----------------+-----------------------+-----------------------------+

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts
>
> ^3^ Predictive distributions calculated from Long-Term multivariate
> longitudinal Bayesian results
>
> [Overall Success: Classical Analysis Results]{.underline}
>
> Table 16 presents a summary of Overall Success rates by study group
> and across time. At the 6-month follow-up, the overall success rate
> for the Control group was statistically significantly lower than the
> overall success rate for the BAK/C group. This finding is consistent
> with the lower rate of fusion success previously reported in the
> Control group at the 6-month follow-up.
>
> Table 16: Long-Term^1^ Overall Success-Classical Analysis Results
> (Restricted^2^ Cohort)

  ----------- ----------- ----------- ----------- ----------- -------------
              BAK/C                   Control                 

              x/n         \%          x/n         \%          p

  6 month     66/114      57.9        32/83       38.6        0.009

  12 month    73/124      58.9        53/93       57.0        Not
                                                              significant

  Long-Term   56/85       65.9        35/66       53.0        Not
                                                              significant
  ----------- ----------- ----------- ----------- ----------- -------------

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later
>
> ^2^ See *Analysis Cohorts* in Section 11.e. for an explanation of the
> Restricted and Unrestricted Cohorts

#### Effectiveness Analysis -- Intent-To-Treat

> An "intent-to-treat" analysis of efficacy data was also performed. All
> missing data (other than missing due to patient death) were considered
> "failures (i.e., included in the denominators of the calculated
> rates). This categorization of unobserved data results in outcome
> rates that are lower than the rates reported in the actual observed
> clinical data. Table 17 presents a summary of the results from the
> intent-to-treat analyses.
>
> Table 17: Long-Term^1^ Effectiveness Analysis --Intent-To-Treat

  ------------------------ ----------- ----------- ----------- -----------
                           BAK/C                   Control     

                           x/n         \%          x/n         \%

  Fusion                                                       

  6 month                  119/160     74.4        77/130      59.2

  12 month                 123/150     82.0        86/122      70.5

  Long-Term                86/101      85.1        66/87       75.9

  Neck Pain                                                    

  6 month                  108/160     67.5        76/130      58.5

  12 month                 108/150     72.0        83/122      68.0

  Long-Term                76/101      75.2        59/87       67.8

  Radicular                                                    

  6 month                  99/160      61.9        66/130      50.8

  12 month                 104/150     69.3        74/122      60.7

  Long-Term                72/101      71.3        54/87       62.1

  Function                                                     

  6 month                  107/160     66.9        74/130      56.9

  12 month                 101/150     67.3        80/122      65.6

  Long-Term                70/101      69.3        51/87       58.6

  Overall Success                                              

  6 month                  66/160      41.3        32/130      24.6

  12 month                 73/150      48.7        53/122      43.4

  Long-Term                56/101      55.4        35//87      40.2
  ------------------------ ----------- ----------- ----------- -----------

> ^1^ Follow-up examination conducted 24 months post-operatively or
> later

### Safety Analyses -- Bayesian Analysis Results

Table 18 presents *freedom from complications* results from the
multivariate longitudinal Bayesian analysis.

Table 19 presents *freedom from complications requiring additional
surgery* results from the multivariate longitudinal Bayesian analysis.

> Table 18: All Complications -- Bayesian Analysis Results

  ------------------------------- ---------- ------------ -----------------------
  Success Measure                 BAK/C^1^   Control^1^   Bayesian Analysis
                                                          Conclusion

  Freedom from All Complications  85.1       74.7         Satisfies criterion for
                                                          equivalence
  ------------------------------- ---------- ------------ -----------------------

^1^ Based on Lifetable Analysis

> Table 19: Complications Requiring Additional Surgery -- Bayesian
> Analysis Results

  -------------------------------- ---------- ------------ -----------------------
  Success Measure                  BAK/C^1^   Control^1^   Bayesian Analysis
                                                           Conclusion

  Freedom from Additional Surgery  93.8       89.2         Satisfies criterion for
  Complications                                            equivalence
  -------------------------------- ---------- ------------ -----------------------

^1^ Based on Lifetable Analysis

### Device Failures and Replacements

No device failures were reported during the course of the clinical
study. No device replacements were required during the course of the
study.

### Conclusions Drawn from the Studies

Using the "24-month or later" outcome data, effectiveness and safety of
BAK/C devices in 1-level patients were established based on equivalence
conclusions for all efficacy and safety criteria.

The results of the clinical study provide reasonable assurance that the
BAK/C Interbody Fusion System is safe and effective for the indicated
patient population.

## Panel Recommendations

> On January 19, 2001, the Orthopedic and Rehabilitation Devices Panel
> recommended unanimously that this PMA be found [approvable with
> conditions]{.underline}. The conditions were as follows:

a.  Limit approval to one-level cases.

b.  Require the sponsor to perform a sensitivity analysis to determine
    effect of high drop-out rate in control group (after randomization,
    but [before]{.underline} implantation).

c.  Require the sponsor to conduct a post-approval study to collect
    5-year post-operative data where post-approval study employs same
    outcome assessments as IDE.

d.  Require the sponsor to evaluate the HA-coating risk/benefit.

e.  Require the sponsor to provide fatigue and static testing of
    post-sterilized HA-coated version of the device.

f.  Require the sponsor to conduct testing on the uncoated devices, or
    justify why the 6mm device is truly worst case and why simple axial,
    compressive loading is representative of physiologic loading.

## CDRH Decision

> CDRH concurred with the Panel's recommendation of January 19, 2001,
> and issued a letter to Sulzer Spine-Tech on March 2, 2001, advising
> that its PMA was approvable subject to the following conditions as
> recommended by the Panel and required by FDA:

a.  Modify the device labeling and Summary of Safety and Effectiveness
    Data to limit approval to one-level cases.

b.  Conduct an additional sensitivity analysis to determine the effect
    of the high drop-out rate in the control group after randomization,
    but before implantation.

c.  Conduct a post-approval study to assess the long-term (5 years
    post-operative) performance of the BAK/C.

d.  Develop an additional post-approval study that focuses on retrieval
    assessment of any BAK/C that is implanted and subsequently removed.

e.  Develop a surgeon training program and describe the methods which
    assure than surgeons can receive this training prior to implanting
    the device in patients.

> In an amendment received by FDA on April 6, 2001, Sulzer Spine-Tech
> submitted the required data. The information provided by Sulzer
> Spine-Tech satisfactorily addressed the above conditions of approval.
> After receipt of this amendment, FDA continued to work with the
> sponsor to finalize product labeling. FDA issued an approval order on
> April 20, 2001.

Inspections of the sponsor's manufacturing facilities and sterilization
sites were completed prior to April 20, 2001. The sites were found to be
in compliance with the device Good Manufacturing Practice regulations.

The PMA for the BAK/C was granted expedited review status on January 29,
1999, because the device potentially represented a clinically meaningful
advantage over existing technology. By eliminating the need to harvest
bone from a second surgical site (e.g., iliac crest), the BAK/C
eliminates the morbidity associated with such harvesting. In addition,
use of autograft bone in a cervical fusion procedure has been shown to
have several advantages over allograft bone (e.g., lower rate of graft
collapse and higher rate of fusion).

## Approval Specifications

> Directions for Use: See product labeling.
>
> Hazard to Health from Use of the Device: See Indications,
> Contraindications, Warnings, and Precautions, and Adverse Reactions in
> the labeling.
>
> Post Approval Requirements and Restrictions: See the Approval Order.