THE LAP-BAND^®^ ADJUSTABLE GASTRIC BANDING SYSTEM

SUMMARY OF SAFETY AND EFFECTIVENESS DATA

**I GENERAL INFORMATION**

> Device Generic Name: Adjustable Silicone Gastric Band, Implanted
>
> Device Trade Name: LAP-BAND^®^ Adjustable Gastric Banding (LAGB^®^)
> System

Applicant's Name and Address: BioEnterics Corporation

> 1035 Cindy Lane
>
> Carpinteria, California 93013

PMA Number: P000008

Date of Panel Recommendation: June 19, 2000

Date of Notice of Approval to the Applicant: June 5, 2001

**II INDICATIONS FOR USE**

The **LAP-BAND System** is indicated for use in weight reduction for
severely obese patients with a Body Mass Index (BMI) of at least 40 or a
BMI of at least 35 with one or more severe comorbid conditions, or those
who are 100 lbs. or more over their estimated ideal weight according to
the 1983 Metropolitan Life Insurance Tables (use the midpoint for medium
frame). It is indicated for use only in severely obese adult patients
who have failed more conservative weight-reduction alternatives, such as
supervised diet, exercise and behavior modification programs. Patients
who elect to have this surgery must make the commitment to accept
significant changes in their eating habits for the rest of their lives.

**III CONTRAINDICATIONS**

The **LAP-BAND System** is contraindicated in:

1.  Patients with inflammatory diseases of the gastrointestinal tract,
    including severe intractable esophagitis, gastric ulceration,
    duodenal ulceration, or specific inflammation such as Crohn's
    disease.

2.  Patients with severe cardiopulmonary diseases or other serious
    organic disease which may make them poor surgical candidates.

3.  Patients with potential upper gastrointestinal bleeding conditions
    such as esophageal or gastric varices or congenital or acquired
    intestinal telangiectases.

4.  Patients with portal hypertension.

5.  Patients with congenital or acquired anomalies of the GI tract such
    as atresias or stenoses.

6.  Patients who have/experience an intra-operative gastric injury
    during the implantation procedure, such as a gastric perforation at
    or near the location of the intended band placement.

7.  Patients with cirrhosis.

8.  Patients with chronic pancreatitis.

9.  Patients who are addicted to alcohol and/or drugs.

10. Non-adult patients (patients under 18 years of age).

11. Patients who have an infection anywhere in their body or where the
    possibility of contamination prior to or during the surgery exists.

12. Patients on chronic, long-term steroid treatment.

13. Patients who are unable or unwilling to comply with dietary
    restrictions, which are required by this procedure.

14. Patients who are known to have, or suspected to have, an allergic
    reaction to materials contained in the system or who have exhibited
    a pain intolerance to implanted devices.

15. Patients or family members with a known diagnosis or pre-existing
    symptoms of autoimmune connective tissue disease such as systemic
    lupus erythematosus or scleroderma.

16. Pregnancy: Placement of the LAP-BAND System is contraindicated for
    patients who currently are or may be pregnant. Patients who become
    pregnant after band placement may require deflation of their bands.

**IV WARNINGS, AND PRECAUTIONS**

Warnings

**WARNING**: Laparoscopic or laparotomic placement of the LAP-BAND
System is major surgery and **death can occu**r

**WARNING:** Failure to secure the band properly may result in its
subsequent displacement and necessitate reoperation.

**WARNING:** A large hiatal hernia may prevent accurate positioning of
the device. Placement of the band should be considered on a case-by-case
basis depending on the severity of the hernia.

**WARNING:** The band should not be sutured to the stomach. Suturing the
band directly to the stomach may result in erosion.

**WARNING:** Patients' emotional and psychological stability should be
evaluated prior to surgery. Gastric banding may be determined to be
inappropriate, in the opinion of the surgeon, for select patients.

**WARNING:** Patients should be advised that the LAP-BAND System is a
long-term implant. Explant and replacement surgery may be indicated at
any time. Medical management of adverse reactions may include
explantation. Revision surgery for explantation and replacement may also
be indicated to achieve patient satisfaction.

**WARNING:** Esophageal distension or dilatation has been reported to
result from stoma obstruction due to over-restriction, due to excessive
band inflation. Patients should not expect to lose weight as fast as
gastric bypass patients, and band inflation should proceed in small
increments. Deflation of the band is recommended if esophageal
dilatation develops.

**WARNING:** Some types of esophageal dysmotility may result in
inadequate weight loss or may result in esophageal dilatation when the
band is inflated and require removal of the band. On the basis of each
patient\'s medical history and symptoms, surgeons should determine
whether esophageal motility function studies are necessary. If these
studies indicate that the patient has esophageal dysmotility, the
increased risks associated with band placement must be considered.

**WARNING:** Patients with Barrett\'s esophagus may have problems
associated with their esophageal pathology that could compromise their
post-surgical course. Use of the band in these patients should be
considered on the basis of each patient's medical history and severity
of symptoms.

**WARNING:** Patient self-adjustment of superficially placed access
ports has been reported. This can result in inappropriate band
tightness, infection and other complications.

Precautions

**CAUTION**: Laparoscopic band placement is an advanced laparoscopic
procedure. Surgeons planning laparoscopic placement must:

1.  Have extensive advanced laparoscopic experience, i.e.,
    fundoplications.

2.  Have previous experience in treating obese patients and have the
    staff and commitment to comply with the long-term follow-up
    requirements of obesity procedures.

3.  Participate in a training program for the LAP-BAND System authorized
    by BioEnterics Corporation or an authorized BioEnterics distributor
    (this is a requirement for use).

4.  Be observed by qualified personnel during their first band
    placements.

5.  Have the equipment and experience necessary to complete the
    procedure via laparotomy, if required.

6.  Be willing to report the results of their experience to further
    improve the surgical treatment of severe obesity.

**CAUTION:** It is the responsibility of the surgeon to advise the
patient of the known risks and complications associated with the
surgical procedure and implant.

**CAUTION:** As with other gastroplasty surgeries, particular care must
be taken during dissection and during implantation of the device to
avoid damage to the gastrointestinal tract. Any damage to the stomach
during the procedure may result in erosion of the device into the GI
tract.

**CAUTION:** During insertion of the calibration tube, care must be
taken to prevent perforation of the esophagus or stomach.

**CAUTION:** In revision procedures the existing staple line may need to
be partially disrupted to avoid having a second point of obstruction
below the band. As with any revision procedure, the possibility of
complications such as erosion and infection is increased. Any damage to
the stomach during the procedure may result in peritonitis and death, or
in late erosion of the device into the GI tract.

**CAUTION:** Care must be taken to place the access port in a stable
position away from areas that may be affected by significant weight
loss, physical activity, or subsequent surgery. Failure to do so may
result in the inability to perform percutaneous band adjustments.

**CAUTION:** Care must be taken during band adjustment to avoid
puncturing the tubing which connects the access port and band, as this
will cause leakage and deflation of the inflatable section.

**CAUTION:** The LAP-BAND System is for single use only. Do not use a
band, access port, needle or calibration tube which appears damaged
(cut, torn, etc.) in any way. Do not use one of them if the package has
been opened or damaged, or if there is any evidence of tampering. If
packaging has been damaged, the product may not be sterile and may cause
an infection.

Do not attempt to clean, re-sterilize or re-use any part of the LAP-BAND
Adjustable Gastric Banding System. The product may be damaged or
distorted if re-sterilized.

**CAUTION:** It is important that special care be used when handling the
device because contaminants such as lint, fingerprints and talc may lead
to a foreign body reaction.

**CAUTION:** Care must be taken to avoid damaging the band, its
inflatable section or tubing, the access port or the calibration tube.
Use only rubber-shod clamps to clamp tubing.

**CAUTION:** The band, access port and calibration tube may be damaged
by sharp objects and manipulation with instruments. A damaged device
must not be implanted. For this reason, a stand-by device should be
available at the time of surgery.

**CAUTION:** Failure to use the tubing end plug during placement of the
band may result in damage to the band tubing during band placement.

**CAUTION:** Do not push the tip of any instrument against the stomach
wall or use excessive electrocautery. Stomach perforation or damage may
result. Stomach perforation may result in peritonitis and death.

**CAUTION:** Over-dissection of the stomach during placement may result
in slippage or erosion of the band and require reoperation.

**CAUTION:** Failure to use an appropriate atraumatic instrument such as
the LAP-BAND Closure Tool to lock the band may result in damage to the
band or injury to surrounding tissues.

**CAUTION:** The band is not intended to be opened laparoscopically with
surgical instruments. Unrecognized damage to the band may result in
subsequent breakage or failure of the device.

**CAUTION:** When adjusting band volume take care to ensure that the
radiographic screen is perpendicular to the needle shaft (the needle
will appear as a dot on the screen). This will facilitate adjustment of
needle position as needed while moving through the tissue to the port.

**CAUTION:** When adjusting band volume use of an inappropriate needle
may cause access port leakage and require re-operation to replace the
port. Use only LAP-BAND System Access Port Needles. Do not use standard
hypodermic needles, as these may cause leaks.

**CAUTION:** When adjusting band volume never enter the access port with
a "syringeless " needle. The fluid in the device is under pressure and
will be released through the needle.

**CAUTION**: When adjusting band volume once the septum is punctured, do
not tilt or rock the needle, as this may cause fluid leakage or damage
to the septum.

**CAUTION:** When adjusting band volume if fluid has been added to
decrease the stoma size, it is important to establish, before discharge,
that the stoma is not too small. Care must be taken during band
adjustments not to add too much saline, thereby closing the gastric
stoma. Check the adjustment by having the patient drink water. If the
patient is unable to swallow, remove some fluid from the port, then
recheck. A physician familiar with the adjustment procedure must be
available for several days post-adjustment to deflate the band in case
of an obstruction.

**CAUTION:** It is the responsibility of the surgeon to advise the
patient of the dietary restrictions which follow this procedure and to
provide diet and behavior modification support. Failure to adhere to the
dietary restrictions may result in obstruction and/or failure to lose
weight.

**CAUTION:** Patients must be carefully counseled on the need for proper
dietary habits. They should be evaluated for nutritional (including
caloric) needs and advised on the proper diet selection. If necessary to
avoid any nutritional deficiencies, the physician may choose to
prescribe appropriate dietary supplements. The appropriate physical
monitoring and dietary counseling should take place regularly.

**CAUTION:** Patients must be cautioned to chew their food thoroughly.
Patients with dentures must be cautioned to be particularly careful to
cut their food into small pieces. Failure to follow these precautions
may result in vomiting, stomal irritation and edema, possibly even
obstruction.

**CAUTION:** Patients must be seen regularly during periods of rapid
weight loss for signs of malnutrition, anemia or other related
complications.

**CAUTION:** Anti-inflammatory agents, which may irritate the stomach,
such as aspirin and non-steroidal anti-inflammatory drugs, should be
used with caution. The use of such medications may be associated with an
increased risk of erosion.

**CAUTION:** Patients who become pregnant or severely ill, or who
require more extensive nutrition, may require deflation of their bands.

**CAUTION:** All patients should have their reproductive areas shielded
during radiography.

**CAUTION:** Insufficient weight loss may be caused by pouch enlargement
or more infrequently band erosion, in which case further inflation of
the band would not be appropriate.

**CAUTION:** Elevated homocysteine levels have been found in patients
actively losing weight after obesity surgery. Supplemental folate and
vitamin B12 may be necessary to maintain normal homocysteine levels.
Elevated homocysteine levels may increase cardiovascular risk and the
risk of neural tube abnormalities.

**CAUTION:** Although there have been no reports of autoimmune disease
with the use of the LAP-BAND System autoimmune diseases, connective
tissue disorders (i.e., systemic lupus erythematosus, scleroderma) have
been reported following long-term implantation of other silicone
devices. These conditions have primarily been hypothesized to be
associated with silicone breast implants. There is currently no
conclusive clinical evidence to substantiate a relationship between
connective-tissue disorders and silicone implants. Definitive long-term
epidemiological studies to further evaluate this possible association
are currently underway. However, the surgeon should be aware that if
autoimmune symptoms develop following implantation, definitive treatment
and/or band removal may be indicated. Likewise, patients who exhibit
preexisting autoimmune symptoms should be carefully evaluated prior to
implantation of the LAP-BAND System and may not be appropriate
candidates (see Contraindications).

**V DEVICE DESCRIPTION**

The LAP-BAND System is a long-term implantable device intended to induce
weight loss in morbidly obese patients by limiting food consumption
(restrictive rather than malabsorption). The device is surgically
implanted, using either a laparoscopic or open procedure, to create a
restricted opening (stoma) and a small gastric pouch to limit food
consumption and induce early satiety. The main components (Figure 1) of
the device are the silicone elastomer band, the access port and
kink-resistant tubing used to connect the other two components. The
inner surface of the silicone band, which is placed around the stomach,
is inflatable and connected by the tubing to the access port (a remote
injection site). The access port is placed in or on the rectus muscle to
permit non-surgical, percutaneous adjustments to the band and thus, the
stoma diameter, using sterile saline.

![](media/image1.png){width="4.0in" height="2.5in"}[Figure 1: LAP-BAND
SYSTEM]{.underline}

The implantable components of the LAP-BAND System:

[Adjustable Gastric Band]{.underline} -- a 13mm-wide, sterile, band
which, when fastened, forms a circular ring. Two sizes are available:
9.75cm and 10.00cm inner circumference. Each size transitions to a
length of kink-resistant tubing which is 50cm in length. The band's
slip-through buckle facilitates laparoscopic placement around the
stomach resulting in the formation of a small gastric pouch and stoma.

[Access Port]{.underline} -- a stainless steel component with a
self-sealing injection site. This sterile port is designed to allow for
post-operative percutaneous adjustment in the stoma diameter. The port
is attached to the inner surface of the gastric band by the
kink-resistant tubing. Saline can be injected into the access port
causing the inner surface of the band to inflate and thus decreasing the
size of the stoma. Saline can also be removed from the LAP-BAND causing
the band to deflate and increasing the size of the stoma. The access
port is available in two sizes (1.2" and 0.98" diameter). The larger
diameter port is a component of the LAP-BAND System while the smaller
port is available as a replacement component.

[Kink-Resistant Tubing]{.underline} -- a 50cm silicone tube (I.D. 0.5",
O.D. 0.13") which connects the inner surface of the gastric band to the
access port.

Other components used during the implantation procedure of the LAP-BAND
System include:

[Calibration Tube Assembly]{.underline} -- a 157cm dual lumen,
translucent, silicone tube with a 13mm-diameter sensor tip and an
inflatable balloon attached to its distal end. The device is inserted
into the patient's esophagus intraoperatively and used to position and
size the stoma of the gastric pouch. The calibration tube is supplied
with the system and is provided clean, non-sterile, and for single use.
The balloon is inflated via an inflation port, which is connected to the
calibration tube's smaller lumen and remains external during the
procedure.

[Silicone End Plug with Stainless Steel Connector]{.underline} -- used
to temporarily seal the System while the band is being positioned around
the stomach. The end plugs are then removed and the other components of
the system connected.

[LAP-BAND Closure Tool]{.underline} (non-sterile, multiple use) --
reusable laparoscopic surgical instrument measuring 50cm in length and
with a diameter of 10mm. It is designed specifically for use when
placing the LAP-BAND. The closure tool is used for "locking" the
LAP-BAND in place around the patient's stomach. It is designed for
autoclave re-sterilization.

[Blunt tip flushing needles]{.underline} -- provided to facilitate
preparation of the System by operating room personnel prior to surgery.
The 16 gauge band priming needle is used to flush and prime the band
tubing and inflatable shell with sterile saline. The 22 gauge access
port flushing needle is used to flush and prime the access port with
sterile saline.

[Access Port Needle]{.underline} -- a 20-gauge, 89mm long, non-coring,
deflected-tip needle designed to penetrate the access port during
postoperative adjustment of the band. Access port needles are provided
sterile and are also available separately.

**VI ALTERNATIVE PRACTICES AND PROCEDURES**

Alternative practices and procedures available for the treatment of
severe obesity (body mass index of greater than 35 kg/m^2^) can be
divided into two categories, non-surgical treatments and obesity
surgery.

**Non-Surgical Treatments (Medical Therapy)**

Non-surgical treatments of obesity include

-   diet, exercise, and behavior modification programs;

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-   prescription weight loss medications; and

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-   other procedures and practices, such as jaw-wiring, hypnosis,
    counseling, psychotherapy, nutritional supplements, etc.

Several reports have suggested a rather high incidence of failure for
severely obese patients to sustain long-term weight loss with any form
of non-surgical treatment.^1,\ 2^

**Obesity Surgery**

Numerous surgical techniques have been developed for the treatment of
severe obesity. The most common obesity surgery procedures performed in
the United States are the Roux-en-Y Gastric Bypass and the Vertical
Banded Gastroplasty.

> [Roux-en-Y Gastric Bypass (GBP)]{.underline}
>
> GBP is the most common of the restrictive-malabsorptive procedures.
> These procedures are considered to be restrictive (a small gastric
> pouch restricting the amount of food consumed) as well as having a
> malabsorptive component (bypassing some part of the intestines). In
> the GBP, the surgeon constructs a proximal gastric pouch, and then
> creates an outlet from the pouch to a limb of the small bowel. This
> results in a bypass of most of the stomach and duodenum.
>
> [Vertical Banded Gastroplasty (VBG)]{.underline}
>
> VBG is one of a group of restrictive obesity procedures which decrease
> the amount of solid food a patient is able to ingest. Rows of staples
> are used to create a small stomach pouch along the lesser curvature of
> the stomach. The pouch outlet (stoma) is reinforced with a copolymer
> band or silicone ring placed through a hole in the stomach.

**VII MARKETING HISTORY**

The LAP-BAND^®^ System has been in use in Europe since 1993. In 1997,
the BioEnterics Corporation LAP-BAND^®^ System was CE-marked. Regulatory
approval has also been obtained in Australia (1994), Canada (1998),
Israel (1997), Mexico (1996) and other countries. No regulatory
approvals have been withdrawn.

Over 50,000 LAP-BAND^®^ Systems have been distributed internationally
and it has been widely reported on in the medical literature.

**VIII POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH**

Adverse events that may result from use of the LAP-BAND System are both
those commonly associated with obesity surgical procedures and others
associated with the device specifically. Potential adverse events
include perforation of the stomach and complications associated with
laparoscopic surgery (e.g., spleen or liver damage, thrombosis and
rupture of the wound, infection, and death). Other risks reported after
gastric restriction procedures include ulceration, gastritis,
gastroesophageal reflux, gas bloat, dysphagia, dehydration,
constipation, nausea and vomiting, and weight regain. Elevated
homocysteine levels have been found in patients actively losing weight
after obesity surgery and may increase cardiovascular risk. In addition,
the developing fetus of pregnant women with elevated homocysteine may be
at risk for neural tube defects. During periods of rapid weight loss
patients may experience malnutrition, anemia or other related
complications, such as the development of cholelithiasis.

Risks associated specifically with the LAP-BAND System are the
possibility of intolerance to the components (foreign body reaction),
mechanical malfunction (leakage and deflation of the inflatable
section), access port site pain and access port displacement, band
slippage/pouch dilatation, band erosion, gastric or esophageal
perforation, stoma obstruction, and esophageal dilatation/dysmotility.
Peritonitis and death can occur either as a consequence of a
gastrointestinal perforation during implantation of the device or as a
result of erosion of the gastric band. The LAP-BAND System is a
long-term implant and the System or a component may need to be either
explanted or replaced. In addition, medical management of adverse events
may necessitate reoperation to revise or explant the device. As with any
revision procedure, the possibility of complications such as erosion and
infection are increased.

In the LAP-BAND System U.S. clinical trial, 266 of 299 (89%) subjects
reported at least one adverse event. Peri-operative adverse events were
reported in 44% of the study subjects. The most commonly reported
peri-operative adverse events were abdominal pain and nausea and/or
vomiting. Eighty-two percent (82%) of subjects reported having one or
more adverse events during the post-operative period. The most commonly
reported adverse events in the post-operative period were nausea and/or
vomiting, gastroesophageal reflux, and band slippage/pouch dilatation.

The most frequently reported adverse events (occurring with a frequency
of ≥5%) are shown in Table 6. Many adverse events were mild and required
no intervention. Serious and severe adverse events were most commonly
addressed either by band adjustment or by reoperation to revise, replace
or remove either a component or the entire LAP-BAND System.

**IX SUMMARY OF PRE-CLINICAL STUDIES**

Testing of product samples was performed on the various components of
the LAP-BAND^®^ System to ensure the product performed according to
product specifications. Testing was performed to evaluate all levels of
the manufacturing process (i.e., raw materials used to fabricate the
device, components from which the device is assembled, the finished
device, the device's packaging, sterilization process of the device, and
product shelf life performance). Laparoscopic placement of the
LAP-BAND^®^ System was evaluated and demonstrated as feasible in a
series of procedures in pigs in 1993.

**Physical Testing**

LAP-BAND^®^ System component mechanical testing was performed for all
components. This data demonstrated that the components met design
specifications and intended use. These components were subjected to
dimensional and visual inspection as well as to break force and tensile
strength testing. The finished assemblies were packaged and subjected to
dry heat sterilization prior to testing. Testing included the following:

-   Fill Tube Patency and Shell Inflation

-   Laparoscopic Device Insertion

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-   Belt Head Insertion Force

-   Shell Crease Fill Volume

-   Shell Burst Volume

-   Locked Buckle and Belt Head Tensile Strength

-   Tear Strength of Punched Buckle Tab Hole

-   Tensile Strength of Adhesive Bond of the Buckle

-   Tensile Strength of Adhesive Bond of the Belt

-   Tubing/Belt Bond Pull Test

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-   Tubing Kink Resistance

-   End-Plug Pullout force

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-   Access Port Multiple Puncture and Over-Pressurization

-   Access Port Assembly Fatigue Testing

Data from these tests demonstrated that finished devices meet the
requirements and specifications for functionality as established in the
LAP-BAND^®^ System product specification.

**Biocompatibility Testing**

The materials and components of the LAP-BAND^®^ System (including the
Access Port, Tubing Connector, the Calibration Tube, Access Port Needle,
and End Plug) that contact the patient are fabricated primarily from
silicone elastomers and polymers. All patient-contacting materials have
been evaluated and tested for biocompatibility and toxicity.

The materials used to fabricate the components in contact with the body
were tested and evaluated for biocompatibility per ISO 10993-1,
"Biological Evaluation of Medical Devices, Part 1: Guidance on Selection
of Tests." The tests were carried out in compliance with 21 CFR Part 58
Good Laboratory Practice Regulations. Materials used in the LAP-BAND^®^
System included silicone elastomers, polysulfone, titanium and stainless
steel. These materials have also been used in other medical device
applications. Biocompatibility test results demonstrated that sterilized
finished devices met the acceptance criteria for each of the tests.

**Packaging and Sterilization**

Dry heat sterilization was validated to provide a sterility assurance
level (SAL) of 10^-6^. Studies demonstrated that the packaging system
maintains the sterile barrier and the devices remain sterile after being
stored on the shelf for up to two years.

Real-time shelf life testing has been conducted; the LAP-BAND System has
a two-year shelf life. Package qualification testing consists of three
phases of evaluation: physical testing of the heat seals, functionality
testing of the LAP-BAND assembly and calibration tube, and sterility
testing of the device.

The LAP-BAND^®^ Closure Tool, a reusable surgical instrument, is
provided non-sterile and designed to be used in the surgical procedure
for band closure. The procedures for cleaning and sterilizing this
instrument have been validated and met acceptance criteria.

**X SUMMARY OF CLINICAL STUDIES**

**[Objectives:]{.underline}**

A clinical study was conducted within the United States under a
significant risk Investigational Device Exemption (IDE) to assess the
safety and effectiveness of the LAP-BAND System in the treatment of
severe obesity.

**[Study design:]{.underline}**

The clinical study was a prospective, multi-center, single-arm trial in
which each subject served as his or her own control.

Subjects were implanted with the LAP-BAND System at 8 clinical sites
within the United States beginning in April 1995. The last subject was
implanted in June 1998. A total of 299 subjects were enrolled in the
study and 292 were implanted with the device. Seven subjects had
previously been implanted with an earlier version of the device, the
Adjustable Silicone Gastric Band (ASGB), and were not included in the
study except for safety analyses of adverse events. Follow-up
evaluations were conducted at 3 weeks, and 3, 6, 9, 12, 18, 24, 30 and
36 months post-implantation.

Evaluation of the safety and effectiveness of the LAP-BAND System was
based on 36-month evaluation of the following clinical endpoints:

[Effectiveness]{.underline}:

1.  percent excess weight loss (%EWL) defined as weight loss divided by
    baseline excess weight. Excess weight was determined from ideal body
    weights based on sex and height- adjusted weight for a medium frame
    according to 1983 Metropolitan Life tables.

2.  absolute weight loss

3.  change in excess weight

4.  change in BMI

5.  change in quality of life (based on Beck Depression Index, the
    Multi-Dimensional Body-Self Relations Questionnaire (MBSR)
    questionnaire, and the RAND SF-36 questionnaire)

[Safety]{.underline}:

Incidence and severity of complications (device and non-device related)

**Patient Selection:**

The inclusion criteria for study enrollment included:

1.  age 18-55

2.  male or female

3.  BMI [\>]{.underline} 40 or at least 100 pounds above ideal weight
    according to the 1983 Metropolitan Life Insurance Tables (medium
    frame)

4.  willingness to comply with the substantial lifelong dietary
    restrictions required by the procedure

5.  history of obesity for at least 5 years

6.  history of failure with non-surgical weight loss methods

7.  willingness to follow protocol requirements, including signed
    informed consent, routine follow-up schedule, completing quality of
    life questionnaires, completing laboratory tests, completing diet
    and behavior modification counseling

8.  residing within a reasonable distance from the investigator's office
    and able to travel to the investigator to complete all routine
    follow-up visits

The exclusion criteria were:

1.  surgery or treatment represents an unreasonable risk to the subject

2.  family or patient history of inflammatory disease of the
    gastrointestinal tract (including ulceration, duodenal ulceration,
    Grade 2-4 esophagitis, or specific inflammation such as Crohn's
    disease or ulcerative colitis)

3.  severe cardiopulmonary disease or other serious organic disease

4.  severe coagulopathy, upper gastro-intestinal bleeding conditions
    such as esophageal or gastric varices, congenital or acquired
    intestinal telangiectasia

5.  congenital or acquired anomalies of the GI tract such as atresias or
    stenoses

6.  severe hiatal hernia

7.  pregnant or has the intention of becoming pregnant in the next 12
    months

8.  alcohol or drug addiction

9.  mentally retarded or emotionally unstable, or exhibits psychological
    characteristics which, in the opinion of the investigator, makes the
    subject a poor candidate for gastric band surgery

10. previous bariatric surgery (except Adjustable Silicone Gastric
    Band), intestinal obstruction or adhesive peritonitis

11. infection anywhere in the body at the time of surgery

12. family or patient history of a known diagnosis or pre-existing
    symptoms of systemic lupus erythematosus, scleroderma, or other
    autoimmune connective tissue disorder

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13. participating in another ongoing clinical trial in which concomitant
    diagnosis or therapeutic intervention would adversely affect the
    integrity of the LAGB clinical trial

Only those patients satisfying the inclusion and exclusion criteria were
allowed to participate. All patients signed an informed consent prior to
being enrolled in the clinical trial.

**[Demographic Data:]{.underline}**

A total of 247 women (85%) and 45 men (15%) met the inclusion criteria
and were implanted with the LAP-BAND device. The majority of patients
enrolled were Caucasian (81%), while African-Americans comprised 15% of
the study population and Hispanics 4%. Almost half the patients enrolled
had hypertension as a comorbidity (43%). Other comorbidities included
gallbladder disease (26%), gastrointestinal diseases (24%), asthma
(16%), and diabetes mellitus (16%).

The average age at time of surgery was 38.8 years (range of 18-56). The
average weight at baseline was 293 pounds (range of 193-475) and the
average BMI at baseline was 47.4 (range of 36.6-74.3). Thirty subjects
had a BMI over 50 at entry. Patients had gained an average of 54 pounds
in the 5 years prior to enrollment.

**[Device Implantation:]{.underline}**

Patients enrolled in the study underwent implantation of the LAP-BAND
System. The band was left empty or minimally inflated at the completion
of the surgery. The first post-operative band adjustment occurred no
sooner than 4-6 weeks, allowing a fibrous capsule to form around the
band (helping to avoid slippage). At the initial adjustment, 1-2cc of
normal saline was added.

The majority of subjects had the device placed laparoscopically (259
patients or 89%). Thirty-three subjects had the device implanted using
an open procedure. Twenty of these 33 subjects were scheduled for the
open procedure while the remaining 13 patients (5%) were converted from
a laparoscopic attempt to open surgery during implantation. The reason
for conversions included difficult anatomy, concomitant surgery,
bleeding, and technical problems. The average hospital length-of-stay
for patients was 1.6 days if performed laparoscopically and 4.4 days if
done by open surgery. Mean surgery time was 178 minutes for
laparoscopically placed devices and 166 minutes for open procedures.

**[Study Results]{.underline}:**

**Patient Accountability**

Two hundred and ninety-nine subjects were enrolled into the study. The
last subject was enrolled in June 1998. Thirty-six month follow-up data
were available for 178 subjects. The remaining 121 subjects were
subdivided into 4 groups as shown in Figure 2 below. Seven (7) subjects
had been previously implanted with the Adjustable Silicone Gastric Band
(ASGB) and were included only in the safety analysis, 46 subjects had
the device explanted, 12 subjects were lost to follow-up and 56 subjects
either missed or had not yet reached the 36 month follow-up visit.

Figure 2: Patient Accountability -- 36 months

[Primary Effectiveness Endpoint:]{.underline}

The primary endpoint for the U.S. clinical trial was percent excess
weight loss (defined as \[baseline wt -- measured wt at the given
timepoint\]/\[baseline wt -- ideal body wt\]). Data representing %EWL is
presented in Table 1 below:

**Table 1: %EWL by Visit**

  ----------- ------- ---------- -------- ------------ ----------- ----------------------
  **Visit**   **N**   **Mean**   **SD**   **Median**   **Range**   **95% Confidence
                                                                   Interval**

  **3 Weeks** 184     9.9        5.0      9.8          -8.1 --     9.2 -- 10.6
                                                       30.3        

  **3         245     18.4       10.0     17.6         -13.5 --    17.2 -- 19.7
  Months**                                             49.0        

  **6         233     26.5       13.8     25.9         -10.3 --    24.7 -- 28.2
  Months**                                             70.0        

  **9         185     30.8       17.1     29.1         -14.9 --    28.4 -- 33.3
  Months**                                             72.5        

  **12        233     34.5       19.0     32.0         -9.0 --     32.1 -- 37.0
  Months**                                             89.3        

  **18        190     36.4       20.4     33.7         -14.4 --    33.5 -- 39.3
  Months**                                             93.1        

  **24        189     37.8       22.5     34.7         -16.8 --    34.6 -- 41.0
  Months**                                             102.7       

  **30        148     37.9       22.9     34.8         -15.5 --    34.2 -- 41.6
  Months**                                             99.3        

  **36        178     36.2       24.6     34.0         -9.8 --     32.6 -- 39.8
  Months**                                             113.0       
  ----------- ------- ---------- -------- ------------ ----------- ----------------------

The %EWL increased between 3 weeks and 18 months and then remained
relatively stable between 18 and 36 months. Patients who reached 36
months of follow-up were able to lose, on average, 36% of their excess
body weight.

It should be noted that by 3 weeks after implantation, before the first
post-operative band adjustment, patients had lost an average of 10% of
their excess body weight. The reason for this is not known. Although not
shown in Table 1, there were no significant differences in %EWL noted
based on age, gender, or race.

Table 2 depicts the number and percentage of patients who were able to
achieve certain benchmark changes in %EWL:

**Table 2: Percentage of Subjects with Subsets of %EWL**

  --------------------------------------- -------------- ----------------
  **Excess weight loss at 3 years**       **%**          **\# patients**

  **Gained more than 5% EWL**             2%             4

  **No change 5% EWL**                    5%             9

  **Lost at least 25% EWL**               62%            110

  **Lost at least 33% EWL**               52%            93

  **Lost at least 50% EWL**               22%            39

  **Lost at least 75% EWL**               10%            18
  --------------------------------------- -------------- ----------------

Table 2 shows that for those patients successfully completing 36 months
of follow-up (178 patients), 22% were able to lose ≥50% of their excess
body weight and an additional 40% lost at least 25% of their excess body
weight. Five percent of patients had minimal or no (±5%EWL) change in
excess body weight and 2% gained more than 5% of their original excess
body weight. Ten percent of patients lost at least 75% of their excess
body weight.

[Secondary Effectiveness Endpoints:]{.underline}

Other study endpoints included absolute weight loss and change in BMI.
These results are depicted respectively in Tables 3 and 4 below:

**Table 3: Mean Weight by Visit (in pounds)**

  -------------- ------- ---------- -------- ------------ ------------ ----------------------
  **Visit**      **N**   **Mean**   **SD**   **Median**   **Range**    **95% Confidence
                                                                       Intervals**

  **Baseline**   288     293.5      53.8     282.8        193.0 --     287.3 -- 299.7
                                                          475.0        

  **3 Weeks**    184     278.8      52.2     267.2        185.4 --     271.3 -- 286.3
                                                          446.0        

  **3 Months**   245     266.2      49.6     257.5        169.3 --     260.0 -- 272.4
                                                          437.0        

  **6 Months**   233     254.5      51.5     244.5        161.8 --     247.9 -- 261.1
                                                          435.0        

  **9 Months**   185     250.6      54.5     240.3        152.0 --     242.8 -- 258.4
                                                          411.5        

  **12 Months**  233     241.8      53.1     240.0        138.0 --     235.0 -- 248.6
                                                          412.0        

  **18 Months**  190     240.5      51.4     236.0        139.0 --     233.2 -- 247.9
                                                          396.5        

  **24 Months**  189     234.5      52.2     230.0        125.0 --     227.1 -- 241.9
                                                          400.0        

  **30 Months**  148     235.4      52.5     233.9        120.0 --     226.9 -- 243.8
                                                          395.1        

  **36 Months**  178     240.6      55.1     239.5        113.0 --     232.5 -- 248.7
                                                          405.6        
  -------------- ------- ---------- -------- ------------ ------------ ----------------------

Table 3 shows that for those patients completing 36 months of follow-up,
the mean body weight decreased by 53 pounds, or 18% (293.5 to 240.6
pounds). Maximum mean weight loss (59 pounds), however, occurred at the
24 month point with a subsequent slight gain in weight between 24 and 36
months.

**Table 4: Mean BMI by Visit**

  -------------- ------- ---------- -------- ------------ ----------- -----------------------
  **Visit**      **N**   **Mean**   **SD**   **Median**   **Range**   **95% Confidence
                                                                      Intervals**

  **Baseline**   288     47.5       7.0      45.8         36.6 --     46.7 -- 48.3
                                                          74.3        

  **3 Weeks**    184     45.1       6.9      43.8         33.5 --     44.1 -- 46.1
                                                          70.6        

  **3 Months**   245     43.2       7.1      41.6         30.9 --     42.3 -- 44.1
                                                          68.1        

  **6 Months**   233     41.2       7.3      40.0         26.5 --     40.3 --42.1
                                                          67.8        

  **9 Months**   185     40.4       7.6      39.7         27.6 --     39.3 -- 41.5
                                                          68.8        

  **12 Months**  233     39.0       7.3      38.3         24.6 --     38.1 -- 40.0
                                                          67.9        

  **18 Months**  190     38.7       7.1      38.7         23.3 --     37.7 -- 39.7
                                                          65.4        

  **24 Months**  189     38.1       7.5      37.9         21.4 --     37.0 -- 39.2
                                                          67.3        

  **30 Months**  148     38.1       7.1      38.7         23.3 --     37.0 -- 39.3
                                                          60.7        

  **36 Months**  178     38.7       7.9      39.0         19.3 --     37.5 -- 39.8
                                                          63.6        
  -------------- ------- ---------- -------- ------------ ----------- -----------------------

Patients enrolled in the study were required to have a BMI of ≥40 for
implantation. The mean BMI at baseline was 47.5. As Table 4 above shows,
the mean BMI decreased to 38.1 at 24 months and 38.7 at 36 months for
those completing follow-up. This represents a 19% reduction in BMI for
those patients by study's end.

Changes in quality of life as measured by the Beck Depression Index,
Multi-Dimensional Body-Self Relations Questionnaire (MBSR) and the RAND
SF-36 scales are depicted in Table 5 below:

> **Table 5: Quality of Life by Visit**

+-----------------------------+----------+-------+---------+---------+
| **Scale**                   | **Ba     |       | **36    |         |
|                             | seline** |       | months  |         |
|                             |          |       | (n      |         |
|                             | **(      |       | =145)** |         |
|                             | n=282)** |       |         |         |
+-----------------------------+----------+-------+---------+---------+
|                             | **Mean** | *     | *       | **SD**  |
|                             |          | *SD** | *Mean** |         |
+-----------------------------+----------+-------+---------+---------+
| **Beck Depression Index**   | 13.5     | 8.5   | 7.0     | 8.3     |
+-----------------------------+----------+-------+---------+---------+
| **MBSR Appearance           | 1.9      | 0.6   | 2.7     | 0.9     |
| Evaluation**                |          |       |         |         |
+-----------------------------+----------+-------+---------+---------+
| **RAND SF-36**              |          |       |         |         |
+-----------------------------+----------+-------+---------+---------+
| **Physical function**       | 49.1     | 24.5  | 76.1    | 25.9    |
+-----------------------------+----------+-------+---------+---------+
| **Role Limit: Physical**    | 39.1     | 40.6  | 78.8    | 35.9    |
+-----------------------------+----------+-------+---------+---------+
| **Role Limit: Emotional**   | 60.6     | 40.3  | 78.2    | 34.6    |
|                             |          |       |         |         |
| **Energy/Fatigue**          | 37.1     | 21.0  | 58.1    | 21.6    |
|                             |          |       |         |         |
| **Emotional Well-Being**    | 65.2     | 18.6  | 71.9    | 20.2    |
|                             |          |       |         |         |
| **Social Function**         | 57.4     | 27.3  | 81.2    | 24.3    |
+-----------------------------+----------+-------+---------+---------+
| **Pain**                    | 58.2     | 25.4  | 78.6    | 24.7    |
+-----------------------------+----------+-------+---------+---------+
| **General Health**          | 52.4     | 23.0  | 71.6    | 19.7    |
|                             |          |       |         |         |
| **Mental Health Composite** | 44.5     | 11.0  | 48.6    | 10.1    |
|                             |          |       |         |         |
| **Physical Health           | 23.6     | 8.5   | 31.4    | 7.6     |
| Composite**                 |          |       |         |         |
+-----------------------------+----------+-------+---------+---------+

Table 5 shows that for patients completing Quality of Life
questionnaires at 36 months, there was an improvement in mean scores for
all categories measured.

[Safety and Adverse Events:]{.underline}

During the course of the US clinical study, 266 (89%) of the subjects
enrolled reported at least one adverse event with 34% reported as being
severe. Although signs and symptoms were recorded separately as
individual adverse events, many of the events were associated with a
"syndrome." For example, patients with band slippage/pouch dilatation
may also have reported nausea, vomiting, and stoma obstruction.

Adverse events were reported for the peri-operative period, 21 days post
LAP-BAND implantation, or the post-operative period. The severity of
each event was rated as mild, moderate or severe and then further rated
as serious or not serious (Figure 3). These were defined as:

> *Mild* -- symptom barely noticeable to the patient; does not affect
> performance or functioning. Prescription drugs not ordinarily needed
> for relief of symptom.
>
> *Moderate* -- symptom of sufficient severity to make patient
> uncomfortable; performance of daily activities affected; patient is
> able to continue in study; treatment of symptoms is needed.
>
> *Severe* -- symptom causes severe discomfort and may be of such
> severity that patient cannot perform daily activities. Severity may
> result in cessation of treatment or require removal of the device, or
> treatment of symptom may be given and/or patient hospitalized.

Adverse events were reported as *serious* if considered to be life
threatening, permanently disabling, unexpected, fatal, requiring
hospitalization, or prolonged hospitalization. All events categorized as
serious in the US clinical study were associated with intervention that
required hospitalization or prolonged hospitalization.

**Figure 3: Classification of Adverse Events**

Adverse events occurring during the study with a frequency of greater
than or equal to 5% are shown in the following table:

Table 6: All Adverse Events in the US Clinical Trial Occurring with
Frequency 5%

+------------------------------+----------+---------------------------+
| **All Adverse Events (Mild,  |          |                           |
| Moderate, Severe)** (N=299)  |          |                           |
|                              |          |                           |
| (≥5%)                        |          |                           |
+------------------------------+----------+---------------------------+
| **Digestive**                | N        | \%                        |
+------------------------------+----------+---------------------------+
| Nausea and/or Vomiting       | 152      | 51                        |
+------------------------------+----------+---------------------------+
| Gastroesophageal Reflux      | 103      | 34                        |
+------------------------------+----------+---------------------------+
| Stoma Obstruction            | 41       | 14                        |
+------------------------------+----------+---------------------------+
| Constipation                 | 27       | 9                         |
+------------------------------+----------+---------------------------+
| Dysphagia                    | 26       | 9                         |
+------------------------------+----------+---------------------------+
| Diarrhea                     | 26       | 9                         |
+------------------------------+----------+---------------------------+
| Abnormal Stools              | 18       | 6                         |
+------------------------------+----------+---------------------------+
| **Body as a Whole**          |          |                           |
+------------------------------+----------+---------------------------+
| Abdominal Pain               | 80       | 27                        |
+------------------------------+----------+---------------------------+
| Asthenia                     | 25       | 8                         |
+------------------------------+----------+---------------------------+
| Incisional Infection         | 21       | 7                         |
+------------------------------+----------+---------------------------+
| Infection                    | 20       | 7                         |
+------------------------------+----------+---------------------------+
| Fever                        | 18       | 6                         |
+------------------------------+----------+---------------------------+
| Hernia                       | 16       | 5                         |
+------------------------------+----------+---------------------------+
| Pain                         | 16       | 5                         |
+------------------------------+----------+---------------------------+
| Chest Pain                   | 15       | 5                         |
+------------------------------+----------+---------------------------+
| Pain Incision                | 14       | 5                         |
+------------------------------+----------+---------------------------+
| **Band-Specific**            |          |                           |
+------------------------------+----------+---------------------------+
| Band Slippage/Pouch Dilation | 72       | 24                        |
+------------------------------+----------+---------------------------+
| Esophageal                   | 29       | 10                        |
| dilatation/dysmotility       |          |                           |
+------------------------------+----------+---------------------------+
| **Metabolic and              |          |                           |
| Nutritional**                |          |                           |
+------------------------------+----------+---------------------------+
| Healing Abnormal             | 23       | 8                         |
+------------------------------+----------+---------------------------+
| **Port-Specific**            |          |                           |
+------------------------------+----------+---------------------------+
| Port Site Pain               | 26       | 9                         |
+------------------------------+----------+---------------------------+
| Port Displacement            | 18       | 6                         |
+------------------------------+----------+---------------------------+
| **Skin and Appendages**      |          |                           |
+------------------------------+----------+---------------------------+
| Alopecia                     | 23       | 8                         |
+------------------------------+----------+---------------------------+

Peri-operative adverse events were reported in 44% of the study
subjects. The most commonly reported peri-operative adverse events were
abdominal pain (10%), nausea and/or vomiting (9%), asthenia (5%), and
incisional infection (5%). Other peri-operative adverse events occurred
in \<5% of the subjects.

Eighty-two percent of subjects reported having one or more adverse
events during the post-operative period. The most commonly reported
adverse events in the post-operative period were: nausea and/or vomiting
(42%), gastroesophageal reflux (32%), band slippage/pouch dilatation
(24%), abdominal pain (18%), stoma obstruction (14%), dysphagia (8%),
alopecia (7%), esophageal dilatation (7%), diarrhea (6%), port site pain
(6%), constipation (5%), port displacement (5%), infection (5%), hernia
(5%), and constipation (5%). Other post-operative adverse events
occurred in less than 5% of the subjects.

The severity of common adverse events (\>5%) was also reported, (see
Table 7 below). The last two columns in the table represent the total
number and percentage of subjects who experienced at least one of the
specified events. The severity scale represents the total number of
events reported; one subject may have experienced a specific event more
than once, and the percentage of all events were rated as mild,
moderate, or severe.

Table 7: Common Adverse Events (\>5%) in the US Clinical Trial by
Severity

<table>
<colgroup>
<col style="width: 27%" />
<col style="width: 8%" />
<col style="width: 0%" />
<col style="width: 8%" />
<col style="width: 8%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 8%" />
<col style="width: 8%" />
</colgroup>
<tbody>
<tr class="odd">
<td></td>
<td colspan="7"><strong>Severity Scale</strong></td>
<td colspan="2"></td>
</tr>
<tr class="even">
<td rowspan="2"><h1 id="adverse-event">Adverse Event </h1></td>
<td colspan="3"><p><strong>Mild</strong></p>
<p><strong>(n*=299)</strong></p></td>
<td colspan="2"><p><strong>Moderate</strong></p>
<p><strong>(n=299)</strong></p></td>
<td colspan="2"><p><strong>Severe</strong></p>
<p><strong>(n=299)</strong></p></td>
<td colspan="2"><strong>Total subjects with at least one event
(n=299)</strong></td>
</tr>
<tr class="odd">
<td><strong>N<sup>**</sup></strong></td>
<td colspan="2"><strong>%</strong></td>
<td><strong>N</strong></td>
<td><strong>%</strong></td>
<td><strong>N</strong></td>
<td><strong>%</strong></td>
<td><strong>n</strong></td>
<td><strong>%</strong></td>
</tr>
<tr class="even">
<td><strong>Nausea/Vomiting</strong></td>
<td colspan="2">128</td>
<td>77.6</td>
<td>32</td>
<td>19.4</td>
<td>5</td>
<td>3.0</td>
<td>152</td>
<td>51</td>
</tr>
<tr class="odd">
<td><strong>GE Reflux</strong></td>
<td colspan="2">72</td>
<td>60.5</td>
<td>39</td>
<td>32.8</td>
<td>8</td>
<td>6.7</td>
<td>103</td>
<td>34</td>
</tr>
<tr class="even">
<td><strong>Abdominal pain</strong></td>
<td colspan="2">55</td>
<td>64.7</td>
<td>23</td>
<td>27.1</td>
<td>7</td>
<td>8.2</td>
<td>80<strong><sup>1</sup></strong></td>
<td>27</td>
</tr>
<tr class="odd">
<td><strong>Slippage/pouch dilatation</strong></td>
<td colspan="2">19</td>
<td>24.4</td>
<td>34</td>
<td>43.6</td>
<td>25</td>
<td>32.1</td>
<td>72</td>
<td>24</td>
</tr>
<tr class="even">
<td><strong>Stoma obstruction</strong></td>
<td colspan="2">6</td>
<td>14.6</td>
<td>18</td>
<td>43.9</td>
<td>17</td>
<td>41.5</td>
<td>41<strong><sup>2</sup></strong></td>
<td>14</td>
</tr>
<tr class="odd">
<td><strong>Dysphagia</strong></td>
<td colspan="2">14</td>
<td>50.0</td>
<td>11</td>
<td>39.3</td>
<td>3</td>
<td>10.7</td>
<td>27</td>
<td>9</td>
</tr>
<tr class="even">
<td><strong>Diarrhea</strong></td>
<td colspan="2">23</td>
<td>85.2</td>
<td>3</td>
<td>11.1</td>
<td>1</td>
<td>3.7</td>
<td>26</td>
<td>9</td>
</tr>
<tr class="odd">
<td><strong>Constipation</strong></td>
<td colspan="2">20</td>
<td>76.9</td>
<td>6</td>
<td>23.1</td>
<td>0</td>
<td>0</td>
<td>27<strong><sup>3</sup></strong></td>
<td>9</td>
</tr>
<tr class="even">
<td><strong>Alopecia</strong></td>
<td colspan="2">20</td>
<td>95.2</td>
<td>1</td>
<td>4.8</td>
<td>0</td>
<td>0</td>
<td>23<strong><sup>4</sup></strong></td>
<td>8</td>
</tr>
<tr class="odd">
<td><strong>Abnormal stool</strong></td>
<td colspan="2">18</td>
<td>100</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>18</td>
<td>6</td>
</tr>
<tr class="even">
<td><strong>Esophageal dilatation/dysmotility</strong></td>
<td colspan="2">7</td>
<td>30.4</td>
<td>8</td>
<td>34.8</td>
<td>8</td>
<td>34.8</td>
<td>29<strong><sup>5</sup></strong></td>
<td>9.7</td>
</tr>
<tr class="odd">
<td><strong>Port displacement</strong></td>
<td colspan="2">5</td>
<td>31.25</td>
<td>9</td>
<td>56.25</td>
<td>2</td>
<td>12.5</td>
<td>18<strong><sup>6</sup></strong></td>
<td>6</td>
</tr>
<tr class="even">
<td><strong>Port site pain</strong></td>
<td colspan="2">19</td>
<td>73.1</td>
<td>6</td>
<td>23.1</td>
<td>1</td>
<td>3.8</td>
<td>26</td>
<td>9</td>
</tr>
<tr class="odd">
<td><strong>Incision infection</strong></td>
<td colspan="2">11</td>
<td>50.0</td>
<td>7</td>
<td>31.8</td>
<td>4</td>
<td>18.2</td>
<td>21</td>
<td>7</td>
</tr>
<tr class="even">
<td><strong>Infection</strong></td>
<td colspan="2">9</td>
<td>40.9</td>
<td>10</td>
<td>45.5</td>
<td>3</td>
<td>13.6</td>
<td>20</td>
<td>7</td>
</tr>
</tbody>
</table>

**\*** n=number of subjects **\*\***N=number of events

^**1**^ severity not reported for 17 events ^**2**^ Severity not
reported for 11 events

^**3**^ 1 Subject with no severity ^**4**^ 2 subjects with no severity

**^5^** Severity not reported for 9 events **^6^** 2 Subjects with no
severity

Some of the commonly reported events associated with the device
necessitated revision in some subjects. Surgery may have been required
to revise, replace or remove any or all components of the device. The
most commonly reported events included:

> [Band slippage and/or pouch dilatation]{.underline} (BS/PD) -- 72
> subjects (24%) reported 78 events of band slippage/pouch dilatation.
> Band slippage refers to slippage of the stomach up through the band
> rather than slippage of the band down lower on the stomach. This
> results in an increase in the proximal pouch and a difference in the
> relative position of the band from where it was implanted. Slippage
> most commonly involves the posterior gastric wall, but can include any
> portion of the stomach. Slippage and pouch dilatation are reported
> together due to the fact that pouch dilatation can result from band
> slippage or it may develop independently, and there is no standard for
> distinguishing between the two events.
>
> The consequences of band slippage varied from subject to subject. In
> some cases, slippage was documented after radiological inspection of
> the band position. If subjects showed no symptoms of slippage, often
> no intervention was deemed necessary or the adjustment of the stoma
> was sufficient to resolve these asymptomatic findings.
>
> Signs and symptoms reported in association with band slippage included
> abdominal pain, nausea and/or vomiting, gastroesophageal reflux,
> dysphagia, and gastric obstruction. For the 56 events reported as
> "resolved," 52% of the subjects recovered after stoma adjustment or no
> intervention, while 48% underwent reoperation, either revision,
> replacement, or explantation of the device.
>
> [Stoma obstruction]{.underline} -- Forty-one subjects (14%) in the US
> clinical trial experienced 52 events of stoma obstruction. Ten
> patients reported multiple episodes. Signs and symptoms associated
> with stoma obstruction included band slippage, asthenia, epigastric
> pain, nausea and vomiting, gastroesophageal reflux, dehydration and
> hypokalemia (secondary to vomiting). Fifty-six percent (23/41) of the
> subjects recovered after stoma adjustment or no intervention; 39%
> (16/41) of the events required surgery (7% revision or replacement and
> 32% band removal), and in 5% (2/41), the method of resolution was not
> reported.
>
> Stoma obstruction and the band slippage/pouch dilatation that may be
> associated with it were the most common causes of LAP-BAND System
> reoperations.
>
> [Abdominal pain]{.underline} -- Eighty subjects (27%) reported 102
> events of abdominal pain. Abdominal pain often accompanied other
> events such as dysphagia, gastroesophageal reflux, or nausea and
> vomiting.
>
> [Dysphagia]{.underline} -- was reported in 26 (9%) of subjects. It was
> most commonly associated with, or related to, stomach/band slippage,
> stoma obstruction, or nausea and/or vomiting.
>
> [Esophageal dilatation/dysmotility]{.underline} -- Twenty nine
> subjects (10%) reported 32 events of either esophageal dilation (21),
> dysmotility (8) or both (3). Esophageal dilatation may be a
> consequence of incorrect band placement, over-restriction, stoma
> obstruction, or excess vomiting. Twenty of the events occurred at one
> site and were believed to be related to band over-inflation. Although
> most events appeared to resolve with deflation of the band, the long
> term consequences of this event are not known.
>
> [Port site pain]{.underline} -- Twenty-six subjects (9%) reported port
> site pain. Seven were reported in the peri-operative period, 18 in the
> post-operative period, and one in both the peri- and post-operative
> periods.
>
> [Port displacement]{.underline} -- was reported in 18 subjects (6%).
> In several of the events the port was suspected on x-ray of being
> displaced but was found not to have been displaced on further
> examination.

Serious adverse events reported with a frequency of less the 5% are
presented below. Except for the 2 reported deaths, these events always
required surgery to remove, replace or revise the device.

## 

> [Deaths]{.underline} -- Two deaths occurred during the course of the
> study. One subject died from "mixed drug intoxication" one week after
> explantation. A second patient died one day after explantation of the
> LAP-BAND and conversion to a Roux-en-Y. Death was due to multiple
> pulmonary emboli. Neither death is believed to have been
> device-related.
>
> [Erosions]{.underline} -- Four subjects (1%) experienced an erosion of
> the band into the gastric lumen. Two of the erosions were considered
> to have been secondary to intra-operative gastric perforations. All
> erosions resolved with explantation of the device.

## [Mechanical malfunctions]{.underline} -- Eight subjects (3%) reported port leakage. The leakage was associated with either cracking of the kink-resistant tubing or disruption of the tubing connection from the port to the band. All of the events resolved after replacement of the port and/or port tubing. In addition, two subjects (0.7%) reported band leakage. One was reported to be due to a leak from a puncture through the thickness of the shell and the other was noted to have resulted from two small holes through the shell. 

> In addition, there were two reports of malfunction (irregular
> inflation) of the calibration tube and one report of breakage of the
> luer-lock connector end of the calibration tube.

[Reoperations -- Revisions, Replacements, and Explants]{.underline}

Twenty-six subjects (9%) underwent 27 surgical revisions involving the
gastric band; one subject had two separate procedures. In 9 of the 27
procedures the band was removed and replaced during a single surgical
procedure. Two subjects were reimplanted with a new band during a
separate surgical procedure. In 16 of the 27 revision procedures the
gastric band was not removed. Most revisions were to correct band
slippage/pouch dilatation. Thirteen of the procedures (48%) were
completed laparoscopically.

## 

## There were twenty-six revisions involving the access port. Thirteen access ports were removed and replaced due to tubing leaks at or near the tubing connections to the port (8/13), port displacement (1/13), or infection (4/13). Nine of these were replaced during the same surgical procedure. The four access ports explanted due to infection were reimplanted at a later time. An additional 13 access ports required revision but did not require removal of the port. The port was repositioned and/or re-sutured in place to correct either misalignment or movement which resulted in an inability to access the port (9/13), pain associated with movement (3/13), or associated infection (1/13). 

A total of 46 subjects (15%) underwent 48 device explantations within 3
years of implantation. An additional twenty-seven subjects (9%) had the
band explanted after the 3 year study period. Fifty-one of the 75
explants (68%) were due to complications, primarily band slippage/pouch
dilatation and/or obstruction 32% (24/75). Other adverse events cited
for explantation of the band included erosion 5% (4/75), infection 4%
(3/75), gastroesophageal reflux and/or dysphagia 11% (8/75), system
leaks 4% (3/75), and esophageal dilatation or dysmotility 7% (5/75). In
the other 24 subjects (32%), insufficient weight loss was cited as the
reason for explantation.

In 45 subjects (60%) the explant procedure was performed
laparoscopically. Approximately one-half of the explanted patients (37)
were converted to a gastric bypass, 3 subjects were converted to a
vertical banded gastrosplasty, and 35 subjects had the system removed
with no other obesity surgery. Nineteen of the subjects had their
obesity surgical procedure (e.g., gastric bypass) performed at the same
time that the study device was removed*.*

[Adhesions]{.underline} -- Forty-two percent (42%) of those patients
undergoing a revision procedure were reported to have developed
adhesions involving the stomach. The exact incidence of adhesions is not
known, as many of the implanted patients did not undergo re-operation.

**XI CONCLUSIONS DRAWN FROM THE STUDIES**

The pre-clinical and clinical data provide reasonable assurance of the
safety and effectiveness of the LAP-BAND^®^ System for use in weight
reduction for severely obese patients, when the system is used in
accordance with its labeling.

Results from the pivotal U.S. clinical trial indicate that, for those
subjects who were able to complete 36 months of follow-up, a mean excess
weight loss (EWL) of 36% and mean overall weight loss of 18% were
achieved. Over half of these subjects (62%) lost more than 25% of their
excess weight and 22% were able to lose more than 50% of their excess
weight. Mean BMI decreased by 19% over the same period of time for these
subjects. In addition, quality of life measures showed general
improvement for subjects at 3 years.

A majority of the subjects implanted (89%) experienced at least one
device-related adverse event. The most common events were
nausea/vomiting (51%), gastroesophageal reflux symptoms (34%), abdominal
pain (27%), and band slippage/pouch dilatation (24%). Twenty-six (26) of
the 292 subjects originally implanted (9%) required surgical device
revision and 46 (16%) required device explantation within 3 years of
implantation. The indications for these re-operations included band
slippage/pouch dilatation, GERD/dysphagia, esophageal dilatation, band
erosion and component leakage.

**[Site-to-Site Variation]{.underline}**

Some site-to-site variations in effectiveness and especially in safety
were observed in the U.S. Clinical Study. Experience with advanced
laparoscopic procedures, attitudes regarding restrictive bariatric
procedures, and patient management and support practices were factors.
For example, one site reported the majority of esophageal dilatations,
which upon review appeared to be related to a difference in
postoperative management. No centers performed more than an average of
two to three procedures a month. This limited and infrequent experience
would be expected to cause and did cause a protracted learning curve in
both laparoscopic placement and patient management, resulting in a
higher incidence of adverse events and reoperations than reported in the
published literature by surgeons with more experience.

**XII PANEL RECOMMENDATION**

The Gastroenterology and Urology Devices Panel met on June 19, 2000, to
consider the safety and effectiveness of the BioEnterics Corporation
LAP-BAND Adjustable Gastric Banding (LAGB) System. The Panel voted six
to four to recommend that the Center for Devices and Radiological Health
(CDRH) not approve the PMA for the LAP-BAND System. They believed that 2
years of follow-up data was not adequate and they recommended at least 3
years of follow-up prior to approval. The study protocol for the U.S.
clinical study called for 3 years of patient follow-up.

**XIII CDRH DECISION**

CDRH agreed with the advisory panel recommendation and sent a major
deficiency letter on August 7, 2000, detailing the data and information
that was still needed. In addition to the 3 years of patient follow-up,
recommendations concerned the labeling and a post-approval study.

The applicant continued its clinical study and on December 26, 2000,
amended the PMA. After review of the additional information, CDRH
determined that there is sufficient safety and effectiveness data to
approve the LAP-BAND Adjustable Gastric Banding System. The sponsor
submitted revised labeling and an outline for the post-approval study
via email and fax. In the post approval study the subjects enrolled in
the U.S. clinical trial will continue to be followed for a total of five
years post implantation. The purpose of the post-approval study is to
obtain additional information on excess weight loss, and adverse events,
primarily esophageal dilatation and band erosion. Subjects will have
continued follow-up for 5 years post-implantation.

**XIV APPROVAL SPECIFICATIONS**

[Directions for Use]{.underline}: See attached Physician Labeling

[Hazards to Health from Use of the Device]{.underline}: See Indications,
Contraindications, Warnings, Precautions, and Adverse Events from
labeling.

[Patient Information:]{.underline} A Surgical Aid in the Treatment of
Morbid Obesity -- LAP-BAND Adjustable Gastric Banding System Information
for Patients

[Post-approval Requirements and Restrictions]{.underline}: See approval
order.

[Training Program]{.underline}

Surgeon participation in a training program authorized by BioEnterics or
by an authorized BioEnterics distributor is required prior to use of the
LAP-BAND System.

**XV REFERENCES**

1.  National Institutes of Health Technology Assessment Conference
    Panel. Methods for Voluntary Weight Loss and Control. *Ann Intern
    Med*. 1993; 119(7):764-770.

2.  National Task Force on the Prevention and Treatment of Obesity.
    Long-term Pharmacotherapy in the Management of Obesity. *JAMA* 1996;
    276(23):1907-1915.