Midterm IDE

Application for
Implantable
Insulin Pump
System
By: Camilo Pascual
Date: 04/02/15
BIOE 689Q

Table of Contents
1.0Device Description

2.0Hazard/Risk Analysis

3.0Pre-Clinical Evaluation

4.0Clinical Trial Design

11

5.0Informed Consent Form

14

6.0References

18

1.0

Device Description
Device: Implantable Insulin Pump System
Components: (1) Implantable Insulin Pump, (2) Programmer Device for dosing and diagnostic,
and (3) Refill Kit.
Implant Site: The pump is implanted and anchored in the abdominal wall. The dispensing
portion of the pump is located in the peritoneal cavity while the refill port traverses the muscle.
Implant Battery Life: 10 years (requires surgical intervention to replace)
Device Class/Pathway: Class III / PMA

Justification for Device Class and Regulatory Pathway

While insulin infusion pumps are considered a Class II device and require a 510(k) to show
substantial equivalence, this is a novel device that is implanted for a 10 year life (>30 days).

This device can be considered life-supporting or life-sustaining, or for a use which is of

substantial importance in preventing impairment of human health, or if the device presents a
potential unreasonable risk of illness or injury, based on the intended population.

It fits into the requirements of 21 CFR 860.93, which defines it as a Class III device.

It matches well with product code LKK (Pump, Infusion, Implanted, Programmable), which
is listed as Class III device and a PMA submission type.

As per 21 CFR 812 and [1], this device would be considered a significant risk, and
therefore, an approved IDE is needed before starting clinical testing in human subjects, in
order to determine the safety and effectiveness of the device.

Indications for Use

Implantable Insulin Pump System
The Implantable Insulin Pump System is intended for continuous intraperitoneal delivery of
basal insulin (at user selectable rates) and administration of insulin boluses (in user selectable
amounts) for the management of diabetes mellitus in persons, twenty-one years of age and older,
requiring insulin.
The Implantable Insulin Pump System consists of the following devices: Implantable Insulin
Pump, Programmer Device, and Refill Kit. The complete system is required for use, except for
the Refill Kit which is supplied to medical professionals, and requires a prescription.
The patient population that may benefit the most from the use of this device includes [2]:

When intensive subcutaneous (SC) insulin treatment using multiple daily insulin injections or
continuous subcutaneous insulin delivery fails to control hyperglycemia (recommended
target for HbA1c in type 1 diabetes mellitus is below 7%) in spite of reinforced patient
education and tight medical follow-up.

Implantable insulin pump treatment, that bypasses SC barrier, has been shown as an effective
therapy in cases where SC insulin treatment fails to reach glucose control because of
defective or highly variable SC absorption of insulin, as diffusion of insulin from skin is not
reliable and results in chronic hyperglycemia.

When the therapeutic target is reached at the cost of a low immediate benefit/risk ratio
(HbA1c level below 7% at expense of recurrent severe hypoglycemia or frequent mild
hypoglycemia).

Patients that have high blood glucose variability with unpredictable hyper-and hypoglycemic
fluctuations, neither related to an irrelevant therapeutic behavior, nor secondary to apparent
skin abnormalities, while using continuous subcutaneous insulin delivery. Some of these
patients may either present recurrent severe hypoglycemic episodes or very frequent non
severe hypoglycemia.

To improve quality of life (patients may complain about multiple daily injections or burden
related to external carriage of pump and catheter).

Device Details
Abdominal Wall /
Implantation Site
Dispensing Port

Anchors
anchors to muscle with
connector
Refill Port / Septum

Figure 1: Drawing of Implantable Insulin Pump with Peritoneal Cavity from [18]. (Not to scale)
Implantable Insulin Pump
The Implantable Insulin Pump is a sterile, battery-operated, and implantable (10-year life)
programmable infusion pump with a rigid titanium housing that dispenses short, frequent pulses
of insulin into the peritoneal space. The pump uses a piston-operated driving mechanism and all
functions of the system (e.g. dosing) are controlled externally using a hand-held, batteryoperated programmer.
The reservoir volume is 15mL and the capacity of the pump allows for enough insulin to supply
the patient for at least three (3) months. The pump is refilled by a medical professional and the
injection area is numbed with a local anesthetic. Withdrawal of leftover insulin in the pump is
also performed. The pump reservoir is under negative pressure which allows the insulin to be
slowly drawn into the reservoir if the needle is placed properly and there is no need to exert
positive pressure on the syringe [6].

Programmer Device
The Implantable Insulin Pump can be programmed with the Programmer Device to provide
continuous delivery of basal insulin at user selectable rates (constant or variable) and administer
insulin boluses in user selectable amounts for meals.
The Programmer Device can also be used to provide diagnostics of the Implantable Insulin
Pump, including information regarding functionalization, volume, battery life, and error alarms.
The Pump/Programmer telemetry is accomplished by the transmission of a series of magnetic
pulses to and from the pump.
LCD Panel

Power Button

Clear Button
CL
R

I/O

Navigation Keys

SE
L

Inquire Button
IN
Q

Figure 2: Drawing of Programmer Device.

Refill Kit
The refill kit is sterile and provides the components and instructions necessary to access the
pump reservoir to empty and fill the Implantable Insulin Pump. The drug chamber is refillable
and is percutaneously accessed via the centrally-located access port using a 22-gauge non-coring
needle.
Insulin*
The Implantable Insulin Pump is intended to be supplied with Insuman Implantable 400 IU/ml
solution for (intraperitoneal) infusion. Insuman Implantable 400 IU/ml is delivered by a
continuous infusion at a basal rate with the remaining 4060% as boluses divided between the
three main meals. The reservoir is filled (and re-filled) with Insuman Implantable 400 IU/ml by
trained medical personnel in hospital using aseptic procedures. Insuman Implantable 400 IU/mL
has to be used under restricted medical prescription, in hospital only and in specialized units [8].
*NOTE: I do not believe that Insuman Implantable has been approved by the FDA (is approved
by EU), so I am unsure if I should be using a different rapid-acting insulin that is FDA-approved,
but not indicated for use for intraperitoneal delivery and/or in the implantable pump reservoir.
Either way, there will be some in vitro and in vivo stability testing and leachables and
extractables testing of the insulin loaded in the pump as part of the pre-clinical evaluation.

Contraindications
Implantation of this device is contraindicated when [2, 7-9]:

a. Patients with severe emotional, psychiatric or substance abuse problems affecting skills in the
management of insulin therapy.
b. People who are unwilling or unable to maintain contact with their healthcare professional.
c. Patients with serious eating disorders that prevent any possible glucose control.
d. Patients whose vision does not allow recognition of pump signals and alarms.
e. Patients with associated severe co-morbidity affecting short-term life expectancy or patient
ability to manage insulin therapy.
f. The presence of infection is known or suspected.
g. The patient's body size or anatomy is insufficient to accommodate the size of the implanted
pump.
h. The patient is known or is suspected to be allergic to materials contained in the pump (e.g.
titanium or silicone material).
i. The patient has exhibited a prior intolerance to implanted devices.
j. Patients that are pregnant or intend to become pregnant.
k. Children who have not yet reached adult size.
l. Exposure to magnetic fields of high intensity (MRI unsafe), very high temperatures, low
atmospheric pressure (extended stays at an altitude higher or equal to 2500 m) or high
atmospheric pressure (underwater diving exceeding 8.50 m).
m. Contraindications relating to Insuman Implantable must be observed and followed per the
approved drug labeling.
NOTE: There were other details of the device that I should have and needed to include in this
section as per guidance documents on infusion pumps [15-17]. Those missing details include,
power requirements and characteristics, more details about the materials of construction (only
noted titanium and silicone in the Contraindications), pump flow rates and profiles and the
accuracy of the device, and safety/alarm functions with indications of error messages. Also, more
engineering drawings would probably be helpful.

2.0

Hazard/Risk Analysis
Potential Adverse Effects of the Device on Health
Below is a list of the potential adverse effects (or risks) related to the use of the Implantable
Insulin Pump System includes, but is not limited to, the following conditions [2, 5, 7-15]:

Infection or other surgical complications at the abdominal implantation site

Insulin underdelivery

Formation of insulin aggregates

Anti-insulin antibody increases

Adverse reaction to pump materials

Defective pump (e.g. pump rupture)

Battery depletion

Bleeding

Body rejection phenomena

Inability to locate septum

Inability to program pump due to programmer failure or loss of telemetry

Inflammation, necrosis, or scarring of skin over implant area

Prolonged pain at the pump site

Programming errors, resulting in over or under dosing

Pump flipping, twisting, migration, or rotation

Pump site pain/soreness

Pump site seroma/hematoma, with or without infection

Pump site skin erosion

Inflammatory mass formation (e.g., granuloma)

Fibrosis

Pump stoppage

Pump failure requiring explant procedure

Refill errors, including incorrect volume, incorrect concentration, difficulty accessing pump
port
Septum leakage

Slow, erratic or fast flow

Software error

Risks of the pump hardware problems with possible hypoglycemia from over-delivery of
insulin due to a hardware defect
Hyperglycemia and ketosis possibly leading to ketoacidosis due to pump failure resulting in
cessation of all insulin delivery due to either a hardware defect or software anomaly
Adverse side effects associated with Insuman Implantable

Potential Benefits of the Device on Health

Below is a list of the potential benefits related to the use of the Implantable Insulin Pump System
in relation to current treatments (multiple daily injections and continuous subcutaneous infusion)
[2-4, 12]:

More physiologic resemblance (hepatic portal insulin delivery)

Metabolic control can be improved

Hypoglycemia episodes can be lessened

Lipid metabolism can be improved

Allows for faster insulin absorption and action and may require smaller doses of insulin

A more rapid clearance of insulin has been suggested as the reason why severe hypoglycemia
occurs less frequently

May also contribute to restoration of glucagon secretion at exercise and after hypoglycemia

Standard deviation of blood glucose levels can be significantly reduced

Potentially would allow for greater control than multiple daily insulin injections or
continuous subcutaneous insulin delivery

Can improve quality of life

Fault Tree Analysis

NOTE: I do not have a lot of experience putting together fault trees, but I just tried to put one
together to address one of the greatest hazards of any infusion pump, free flow of drug. In this
case, free flow of insulin from the implanted pump would most likely result in a diabetic coma
and/or the death of the patient.
Free-Flow of
Insulin

Pump
rupture
s

Valve or
septum is
broken
Softwar
e error

User
error

Faulty
supplies

Quality
testing
fails

Faulty
manufacturing
process

3.0

Pre-Clinical Evaluation
No testing data will be provided in this section (was not required), but details will be provided
regarding the Pre-Clinical Evaluation studies that were performed [7-9, 15-17, 19].

Performance Verification Studies

Product and component verification testing was completed to demonstrate that the finished
device performs in accordance with design specifications. This section provides an overview of
performance qualifications that were performed.

Pump qualifications would include flow accuracy determination especially at the bodys
temperature range (35-40C), at different pressure ranges or altitudes, and at different fluid
viscosities (using different insulins or fluids).

Reservoir qualification through pressure vs. volume testing.

Pump life testing which includes the effect on flow rates of the 10-year life span and battery
life testing.

Cadaver studies to confirm the placement and implantation procedure for the pump.

Testing of the components, such as determination of the average septum puncture life to test
its durability and verification of valve.

Alarm testing, which includes the Programmer Device, would also be performed to confirm
the correct error messages are being displayed for alarm events, such as occlusions, low
battery, and low volume.

Software verification and validation of the Programmer Device was performed and showed
acceptable unresolved anomalies and information security.

Drug Compatibility and Stability Studies

The pump is delivering insulin (Insuman Implantable) so studies were performed to verify and
validate that our pump does not adversely affect the insulin being delivered and that the insulin
does not adversely affect our pump. This section provides an overview of drug compatibility and
stability studies that were performed.

In-vitro drug stability and compatibility testing performed on the pump indicates that
Insuman Implantable is stable for 90 days.

In-vitro stability was evaluated with the pump operating at 37C over subsequent refill
periods. The pump was evaluated regarding flow performance and stability of Insuman
Implantable.

As part of the animal studies, in-vivo samples were taken and an analysis was performed of
the solutions recovered from the pump reservoir before a refill.

The data also indicates that the sodium hydroxide (NaOH) rinse procedure is suitable to
prevent pump blockage by fibril formation.

Leachables and extractables testing were performed according to ISO 10993-13, ISO 1099315, ISO 10993-16, and ISO 10993-18.

The studies observed acceptable results for drug assay, degradation products, impurities,
leachables, extractables, and performance of the pump.

Electrical and Environmental Safety Studies

Review of the electronic components, including battery, valve, programmer, and electronic
assemblies, demonstrated that electrical safety was adequately demonstrated through the life of
the device. This section provides an overview of electrical and environmental studies that were
performed.

Electromagnetic compatibility between the pump and Programmer Device was demonstrated
by meeting the applicable standards in ANSI/AAMI ES606011 (Medical electrical equipment
Part I: General requirements for basic safety and essential performance) and IEC 60601-111 (Medical electrical equipment Part 1-11: General requirements for basic safety and
essential performance Collateral Standard: Requirements for medical electrical equipment
and medical electrical systems used in the home healthcare environment).

Demonstrated that the device will operate within its specification when exposed to
electromagnetic interference at the levels in the excess of those expected in normal use
environment.

Magnetic Resonance Imaging (MRI) compatibility showed that the device is MRI unsafe.

Computed Tomography (CT) compatibility evaluated the device and demonstrated its
compatibility with CT scans.

Biocompatibility Studies
This device is an implanted intraperitoneal pump, and is categorized as a permanent implant in
contact with tissue/bone. Biocompatibility studies were conducted to ensure that the components
and the finished device are safe and perform in accordance with the design specifications.
Biocompatibility testing was performed to evaluate the materials that make direct contact with
tissue/bone. The ISO 10993 Standard and the U.S. FDA Blue Book Memorandum #G95-1 were
used as guidance in determining the appropriate tests for the device. The following
biocompatibility tests were performed.

Genotoxicity, Carcinogenicity, and Reproductive Toxicity as per ISO 10993-3.

Cytotoxicity as per ISO 10993-5.

Implantation and Muscle Implantation as per ISO 10993-6.

Irritation/Intracutaneous and Sensitization as per ISO 10993-10.

Pyrogenicity, Subchronic and Chronic Toxicity, and Acute Systemic Toxicity as per ISO
10993-11.

Package and Sterilization Studies

Qualification testing of the pump packaging consisted of environmental stress conditioning
including temperature & humidity conditions, vibration, and drop testing. Environment exposure
testing confirmed the pump remains functional after temperature, vibration, and shock exposures

10

are applied to the pump. These evaluations demonstrated packaging is acceptable to simulated
shipping and transit conditions.
Validation of the pump sterilization (Moist Heat) demonstrates that the sterilization processes
achieve a sterility assurance level of 10 -6, which meets the standards for a critical device
(introduced directly into blood stream or other normally sterile areas of the body).
The pump has a 2-year shelf life.

Human Factors/Usability Studies

Simulated Use Testing was performed to validate that the intended design of the pump meets the
needs of the user. The testing involved a review of the instructions for use, the Programmer
Devices technical manual, the implantation of the pump, programming the pump for various
operations, as well as accessing the pump once implanted.
The final validation study included twenty (20) representative users. Users interacted with the
Programmer Device within use scenarios that required performance of all essential tasks. The
human factors study was designed in accordance the FDA's Human Factors guidance: Medical
Device Use Safety: Incorporating Human Factors in the Risk Management.

Animal Studies
Animal studies were performed in pigs to demonstrate the safety and effectiveness of
intraperitoneal delivery of insulin using the implanted pump. Other items that were evaluated
included,

Ease of implantation regarding the size/shape of the pump and its fixation in the abdominal
wall.

Instructions for use regarding the surgical implantation of the pump.

Refill and rinsing procedure for the pump.

Pump performance and use with the Programmer Device.

Post-implant histological assessment of tissue response to the implanted pump.

11

4.0

Clinical Trial Design

NOTE: I designed the clinical trial under the presumption that the insulin (Insuman
Implantable) is FDA-approved, as I imagine that if the drug or biologic was not approved, then
it would require multiple phase trials and/or more subjects to also test the safety and efficacy of
the administered drug.
Objective

To study the safety and efficacy of the Implantable Insulin Pump System for the delivery of
Insuman Implantable into the intraperitoneal space, as programmed.
Allocation: Non-Randomized
Classification: Safety/Efficacy Study

Study Design

Intervention Model: Single Group Assignment

Masking: Open Label

Trial
Organization

Primary Purpose: Treatment

The study is expected to last 12-15 months for each subject. There will be an estimated 15 clinic
visits, 2 phone visits, and one hospital stay for 2-3 days after the initial screening. The visits will
include the 3-monthly refills and data collections.
Investigational centers (10 sites) will be selected across the United States.

Comparison
Group
Study
Population
Sample Size

Endpoints

Statistical
Analysis

Active Treatment Control (device subjects serve as own control).

Adults (21 years) with type 1 diabetes mellitus that meet the inclusion/exclusion criteria.
Subjects will be grouped by baseline demographics: age, ethnicity, body mass index (BMI),
gender, and duration of diabetes and hypoglycemic awareness.
Up to 380 subjects will be enrolled so that there will be 300 subjects who are eligible to
participate in the study.
Primary endpoint: The overall mean change in HbA1c from baseline.
Secondary endpoints: Frequency of Hypoglycemia Events, Weight Gain, Cholesterol,
Standard Deviation of Glucose Levels, Meaningful Reduction of Insulin Requirements, AntiInsulin Antibody Assessment.
Safety endpoints: Serious Adverse Events (SAE), Unanticipated Device Effects (UADE),
Incidence of Severe Hypoglycemia, Incidence of Severe Hyperglycemia, Incidence of Diabetic
Ketoacidosis (DKA).
For the primary endpoint will be compared by a superiority test with an HbA1c margin of 0.4%
and a significance level of 0.05 (two-sided).
Mean comparisons to baseline by 95% confidence two-sided t-test for BMI, LDL Cholesterol,
CGM Metrics, Insulin Doses, Anti-Insulin Antibodies, and Frequency of Hypoglycemia for the
past 2 weeks.

12

Inclusion
Criteria

Exclusion
Criteria

a.

Subject is between the ages of 21 - 60 years old;

b.

Subject has a life expectancy of >1 year;

c.

A clinical diagnosis of type 1 diabetes as determined by the investigator, for a minimum of 12

months duration;

d.

Subject has an HbA1c value greater than 7.0% at time of enrollment, as measured during the
screening visit and/or suffers from recurrent severe hypoglycemia or frequent mild
hypoglycemia;

e.

Subject has glucose ineffectively controlled by multiple daily injections or continuous

subcutaneous infusion;

f.

Subject is able to provide written informed consent to participate in the study;

g.

Subject is considered by the investigator to be a medically and psychologically appropriate

candidate for pump implantation;

h.
a.

Subject is willing to follow protocol and procedures for study.

Subject has a systemic infection;

b.

Subjects anatomy is not large enough to accommodate the pumps size and weight;

c.

Subject is pregnant or is of child-bearing potential and not employing effective birth control;

d.

Subject has known allergies or sensitivities to pump materials (e.g. titanium or silicone);

e.

Subject has known allergies to Insuman Implantable or would be contraindicated for it, based
on the drug labeling (e.g. impaired renal or hepatic function);

f.

Subject has a visual impairment that prevents proper handling of the device.

g.

Subject has a major coexisting medical condition (such as a heart condition), that in the
opinion of the investigator, contraindicates an implantable pump;

h.

Subject has other implanted cardiac electronic devices;

i.Subject is to require MRI-evaluation post-implantation;

j.

Subject has an occupation where he/she would be exposed to high current industrial
equipment, powerful magnets or transmitting towers, such as, electricians, electrical engineers
or MRI technicians;

k.

Subject has a history of diagnosed medical eating disorder;

l.Subject has a history of known illicit drug abuse;

m. Subject is unable or unwilling to participate in all necessary study activities due to physical or
mental limitations;
n.

Subject is unable or unwilling to return for all required follow-up visits;

o.

Subject is unable or unwilling to sign the informed consent document.

13

The study phases are as follows:

Screening visit to see if you are eligible for the study

Data collection with CGM is started and surgery is scheduled within 3 months (visit 1)

Implantation of pump and training (hospital stay)

Call 2 weeks post-implantation (phone visit 1)

Call 4 weeks post-implantation (phone visit 2)

Data collection visit about 1.5 months post-implantation and CGM will be started (visit
2)

Procedures

Approximately a week later the CGM is returned (visit 3)

Tests and refill of pump 3 months post-implantation (visit 4)

Data collection visit about 1.5 months after first refill and CGM will be started (visit 5)

Approximately a week later the CGM is returned (visit 6)

Tests and refill of pump 6 months after implantation (visit 7)

Data collection visit about 1.5 months after second refill and CGM will be started (visit
8)

Approximately a week later the CGM is returned (visit 9)

Tests and rinse and refill of pump 9 months after implantation (visit 10)

Data collection visit about 1.5 months after third refill and CGM will be started (visit 11)

Approximately a week later the CGM is returned (visit 12)

Tests and refill of pump 12 months after implantation (visit 13)

Data collection visit about 1.5 months after fourth refill and CGM will be started (visit
14)

Final study clinic visit: Approximately a week later the CGM is returned (visit 15)
NOTE: After research is completed, subjects will still be cared for with the implanted pump,
having visits for refills and tests every 3 months. This long-term follow up will last until the
subject chooses to withdraw, the pump malfunctions, the FDA approves the pump for regular care,
or the company no longer supports the pump. If the subject is no longer taking part in the study,
we will have the pump removed from their body.

14

5.0

Informed Consent Form

PART I: Information Sheet
Introduction
I am ________________, working for the _______________ Research Institute. We are doing research
on diabetes mellitus, which is very common in this country. I am going to give you information and invite
you to be part of this research. You do not have to decide today whether or not you will participate in the
research. Before you decide, you can talk to anyone you feel comfortable with about the research.
There may be some words that you do not understand. Please ask me to stop as we go through the
information and I will take time to explain. If you have questions later, you can ask them of me, the study
doctor or the staff.
Purpose of the research
Diabetes mellitus is a common disease. The devices that are currently used to help people with diabetes
mellitus are not as good as we would like them to be. In fact, some people have a hard time reducing their
A1C level and frequency of hypoglycemic episodes with current treatments. There is a new device which
may work better. The reason we are doing this research is to find out if the new device is better than
current treatments which are currently being used.
Type of Research Intervention
This research will involve an implantation in your abdominal wall, as well as two phone visits and fifteen
follow-up visits to the clinic. You will still be cared for with the implanted pump, having visits for refills
and tests every 3 months. Long-term follow ups will last until you choose to withdraw, the pump
malfunctions, the FDA approves the pump for regular care, or the company no longer supports the pump.
If you are no longer taking part in the study, the pump will be removed from your body.
Participant selection
We are inviting all adults with diabetes mellitus who attend clinic ______________ and have poor
glycemic control to participate in the research on this device.
Voluntary Participation
Your participation in this research is entirely voluntary. It is your choice whether to participate or not.
Whether you choose to participate or not, all the services you receive at this clinic will continue and
nothing will change. If you choose not to participate in this research project, you will offered the
treatment that is routinely offered in this clinic/hospital for diabetes mellitus, and we will tell you more
about it later. You may change your mind later and stop participating even if you agreed earlier, but if you
are no longer taking part in the study, the pump will be removed from your body.
Information on the Trial Device [Implantable Insulin Pump System]
The device we are testing in this research is called Implantable Insulin Pump System. It has been tested in
before in animals. We now want to test the device on people who have diabetes mellitus. This research is
called a safety/efficacy trial.
The device Implantable Insulin Pump System is made by Company DB Pumps. You should know that it
has a few side effects. One of the side effects, or problems, is that you may feel pain/soreness for the first
few weeks after being implanted with the device. We know of no other problem or risks.

15

Procedures and Protocol

A. Unfamiliar Procedures
This section should be included if there may be procedures which are not familiar to the participant.

B. Description of the Process

During the research you make fifteen visits to the clinic.

Duration
The research takes place over 12-15 months in total. During that time, it will be necessary for you to have
a hospital stay for 2-3 days, to make 2 phone calls, for 10 minutes each call, and to come to the
clinic/hospital/health facility 15 days, for 30 minutes each day. We will provide long-term follow ups until
you choose to withdraw, the pump malfunctions, the FDA approves the pump for regular care, or the
company no longer supports the pump.
In total, you will be asked to come 15 times to the clinic in 12 months. At the end of 12-15 months, the
research will be finished and you can return every 3 months for refills.
Side Effects

Risks
By participating in this research it is possible that you will be at greater risk than you would otherwise be.
There is, for example, a risk that your disease will not get better and that the new device doesn't work
even as well as the old one. If, however, the device is not working and your A1C level does not improve
we will use standard treatments to make you more comfortable.
While the possibility of this happening is very low, you should still be aware of the possibility. We will
try to decrease the chances of this event occurring, but if something unexpected happens, we will provide
you with $750.
Benefits
If you participate in this research, you will have the following benefits: any interim illnesses will be
treated at no charge to you. If your child falls sick during this period he/she will be treated free of charge.
There may not be any benefit for you but your participation is likely to help us find the answer to the
research question. There may not be any benefit to the society at this stage of the research, but future
generations are likely to benefit.

16

Reimbursements
We will give you $500 to pay for your travel to the clinic/parking and we will give you $750 for lost work
time. You will not be given any other money or gifts to take part in this research.
Confidentiality
With this research, something out of the ordinary is being done in your community. It is possible that if
others in the community are aware that you are participating, they may ask you questions. We will not be
sharing the identity of those participating in the research.
The information that we collect from this research project will be kept confidential. Information about
you that will be collected during the research will be put away and no-one but the researchers will be able
to see it. Any information about you will have a number on it instead of your name. Only the researchers
will know what your number is and we will lock that information up with a lock and key. It will not be
shared with or given to anyone except [name who will have access to the information, such as research
sponsors, DSMB board, your clinician, etc.].
Sharing the Results
The knowledge that we get from doing this research will be shared with you through community meetings
before it is made widely available to the public. Confidential information will not be shared. There will be
small meetings in the community and these will be announced. After these meetings, we may publish the
results in order that other interested people may learn from our research.
Right to Refuse or Withdraw
You do not have to take part in this research if you do not wish to do so and refusing to participate will
not affect your treatment at this clinic in any way. You will still have all the benefits that you would
otherwise have at this clinic. You may stop participating in the research at any time that you wish without
losing any of your rights as a patient here, but if you are no longer taking part in the study, the pump will
be removed from your body. Your treatment at this clinic will not be affected in any way.)
Alternatives to Participating
If you do not wish to take part in the research, you will be provided with the established standard
treatment available at the center/institute/hospital. People who have diabetes mellitus are treated with
multiple daily injections or continuous delivery from a pump and catheter.
Who to Contact
If you have any questions you may ask them now or later, even after the study has started. If you wish to
ask questions later, you may contact any of the following: [name, address/telephone number/e-mail]
This proposal has been reviewed and approved by [name of the local IRB], which is a committee whose
task it is to make sure that research participants are protected from harm. If you wish to find out more
about the IRB, contact [name, address, telephone number]. It has also been reviewed by the Ethics
Review Committee of the World Health Organization (WHO), which is funding/sponsoring/supporting
the study.

You can ask me any more questions about any part of the research study, if you wish to. Do you
have any questions?

17

PART II: Certificate of Consent

I have read the foregoing information, or it has been read to me. I have had the opportunity to ask
questions about it and any questions that I have asked have been answered to my satisfaction. I consent
voluntarily to participate as a participant in this research.
Print Name of Participant__________________________________________
Signature of Participant ___________________________________________
Date __________________________
Day/month/year
If illiterate
I have witnessed the accurate reading of the consent form to the potential participant, and the individual
has had the opportunity to ask questions. I confirm that the individual has given consent freely.
Print name of witness_____________________

AND

Thumb print of participant

Signature of witness ______________________

Date ________________________
Day/month/year

Statement by the researcher/person taking consent

I have accurately read out the information sheet to the potential participant, and to the best of my
ability made sure that the participant understands that the following will be done:
1.
2.
3.
I confirm that the participant was given an opportunity to ask questions about the study, and all
the questions asked by the participant have been answered correctly and to the best of my ability.
I confirm that the individual has not been coerced into giving consent, and the consent has been
given freely and voluntarily.
A copy of this ICF has been provided to the participant.
Print Name of Researcher/person taking the consent___________________________________
Signature of Researcher/person taking the consent____________________________________
Date ___________________________
Day/month/year

18

6.0

References
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Document No. UCM126418.
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insulin infusion and subcutaneous insulin therapy among patients with poorly controlled
type 1 diabetes mellitus: Favourable effects on hypoglycaemic episodes. Diabetes
Research and Clinical Practice (2014), 106(2):256-263.
[4] van Dijk P.R. et al. Continuous intraperitoneal insulin infusion in type 1 diabetes: a 6-year
post-trial follow-up. BMC Endocrine Disorders (2014), 14(30).
[5] Haveman J.W. et al. Surgical aspects and complications of continuous intraperitoneal
insulin infusion with an implantable pump. Langenbecks Arch Surg. (2010) 395(1):6571.
[6] Witkowski C.J. et al. The Implantable Peritoneal PumpA Patients Perspective. J
Diabetes Sci Technol (2008), 2(4):703706.
[7] Medasys, Inc. Summary of Safety and Effectiveness Data for Implantable Infusion Pump
Prometra Programmable Infusion Pump System. FDA (2012), PMA No. P080012.
[8] Committee for Medicinal Products for Human Use (CHMP). Assessment Report for
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EMEA/H/C/000201/X/0091.
[9] Medtronic MiniMed. Summary of Safety and Effectiveness Data Artificial Pancreas Device
System, Threshold Suspend MiniMed 530G System. FDA (2013), PMA No. P120010.
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Obstruction During Peritoneal Insulin Delivery With an Implantable Pump. Diabetes Care
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[11] Jeandidier N. et al. Comparison of Antigenicity of Hoechst 21PH Insulin Using Either
Implantable Intraperitoneal Pump or Subcutaneous External Pump Infusion in Type 1
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[12] Saudek C.D. et al. Insulin Pumps: Hopes and Expectations. FDA/NIH Joint Symposium
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[13] TPLC Total Product Life Cycle. Device: Pump, Infusion, Implanted, Programmable.
Product Code: LKK. Device Class: 3.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTPLC/tplc.cfm?id=2589
[14] TPLC Total Product Life Cycle. Device: Pump, Infusion, Insulin. Product Code: LZG.
Device Class: 2. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfTPLC/tplc.cfm?
id=2479
[15] CDRH. Infusion Pumps Total Product Life Cycle - Guidance for Industry and FDA Staff.
FDA (2014), Guidance Document No. UCM209337.
[16] CDRH. Guidance on 510(k) Submissions for Implanted Infusion Ports. FDA (1990),
Guidance Document No. UCM081374.
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[17] CDRH. Guidance on the Content of Premarket Notification [510(k)] Submissions for
External Infusion Pumps. FDA (1993), Guidance Document No. UCM081337.
[18] http://web.stanford.edu/dept/radiology/radiologysite/images/Med%20students
%203,%20peritoneal%20cavity/Peritoneal%20cavity,%20normal%20+%20malignant
%20ascites%20(4).png
[19] CDRH. Use of International Standard ISO- 10993, "Biological Evaluation of Medical
Devices Part 1: Evaluation 3 and Testing" - Draft Guidance for Industry and Food and Drug
Administration Staff. FDA (2013), Guidance Document No. UCM348890.
[20] CDER. Guidance for Industry - Diabetes Mellitus: Developing Drugs and Therapeutic
Biologics for Treatment and Prevention Draft Guidance. FDA (2008), Guidance
Document No. UCM071624.
[21] Zhang Y. et al. A Hazard Analysis for a Generic Insulin Infusion Pump. J Diabetes Sci
Technol (2010), 4(2):263283.

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