**APPENDIX I: INFORMED CONSENT: Protocol #4167, BB IND 11184**

**INFORMED CONSENT FOR**

**USE OF DIPHTHERIA ANTITOXIN (DAT) FOR SUSPECTED DIPHTHERIA CASES**

**Investigational New Drug (IND) BB 11184**

**IRB \# 4167**

*[Flesch-Kincaid: 7.8]{.underline}*

**INFORMED CONSENT**

Your doctor suspects that you/your child have diphtheria. Your doctor
has decided that you need diphtheria antitoxin (DAT) and to give it to
you/your child. The Food and Drug Administration (FDA) has not approved
DAT for diphtheria treatment in this country. The Centers for Disease
Control and Prevention (CDC) and your State Health Department can
provide DAT for emergency treatment of diphtheria. So, we are offering
you/your child treatment with investigational DAT. Diphtheria antitoxin
is obtained from horse serum. The company that makes DAT has tested the
product to make sure that it is potent for the specified and
FDA-approved shelf life.

**BACKGROUND**

Diphtheria is a serious illness caused by a toxin (poison). This toxin
is produced by a bacterium called *Corynebacterium diphtheriae*. The
toxin causes life-threatening illness in many people infected with the
bacteria. This is because the toxin kills many types of human cells,
mainly those in a person's throat, windpipe, heart, and nerves. Harm to
these cells can lead to blockage of the windpipe, heart damage, and
paralysis of many nerves. This can lead to death in up to 50% of
untreated patients. It can also disable those who survive. Airway
blockage can occur within the first week of illness. But, the signs of
heart and nerve damage most often show in the second or third week.

Use of DAT is vital to treat diphtheria. DAT can greatly lower the risk
of lasting health problems or very severe outcomes. DAT works better if
given as soon as the doctor suspects diphtheria. Signs of diphtheria
usually show slowly from 1 to 5 days after infection. These signs
include fever, sore throat, problems swallowing, widespread weakness,
and, at times, problems breathing. Often, but not always, the doctor can
see a gray, white, or yellow patch (membrane) in the throat or tonsils.

Until January 1997, there was a FDA-approved DAT in the U.S., but the
supply of this product has been used up. Since there are so few cases of
diphtheria in the U.S. each year, the company decided to stop making it.
There is DAT available from a foreign country. FDA considers it
"investigational" because it is not licensed in this country. This DAT
has been used for years to successfully treat diphtheria patients in
other countries. It is like the product that was made in the U.S.
previously except that it is made by a different company. We are
offering this product to you/your child. In the judgment of your doctor,
it is the best treatment you/your child can get.

**WHAT IS THE PURPOSE OF THIS TREATMENT?**

You/your child may have been exposed to diphtheria. We are offering DAT
to you/your child because your doctor suspects you/your child have
diphtheria. Without DAT, diphtheria can get worse and life-threatening
complications can result. Because DAT is made from horse serum, you/your
child may have an allergic reaction after receiving it. Your doctor will
give you/your child a skin test. This is to see if you/your child could
have an allergy to DAT. For this test the doctor will inject a small
amount (less than a drop) of DAT into the skin with a needle. The doctor
will check after 20 minutes to see if your/your child's skin gets red or
swells. If the skin test is positive for redness and swelling, the
doctor may give you/your child DAT in very small doses to lower the risk
of an allergic reaction. The doctor may also give you/your child other
medicines to lower the risk.

Your/your child's doctor will give you/your child DAT with a needle
directly into a vein or muscle. The doctor will take samples (using a
swab that looks like a Q-tip) from your/your child's throat and nose
before treatment. Also, if there is a patch on your/your child's throat,
the doctor may need to scrape off a small piece of this patch and sent
to the lab. These tests allow us to confirm that you/your child have
diphtheria. You/your child's doctor will send the samples and any
scraping to the CDC so we can culture the bacteria and find the toxin.

**ARE THERE ANY BENEFITS?**

DAT can reduce the bad effects of diphtheria toxin. It does not reverse
any problems that have already happened. DAT will prevent later problems
if it is given early in the illness. Without DAT, severe problems due to
diphtheria can happen. About 3 out of 10 persons with diphtheria do not
survive without DAT.

**ARE THERE ANY RISKS?**

Treatment with DAT is not without risk. As with all treatment**,** there
is a slight chance that there are some risks that we do not know about.

The risks of getting any medicine by vein include brief pain, bleeding,
and bruising of the skin around the site where the needle went in. Other
risks are soreness and swelling at that site and possible infection.

You/your child may react to DAT in a number of ways. These include fever
and chills, usually within the first 24 hours. These will go away by
taking aspirin or Tylenol (aspirin should not be used in children due to
risk of Reye syndrome).

A few people (\<1%) may have a more serious allergic reaction called
*anaphylaxis*. It can happen in people who are allergic to horse
products. Most of them do not know they are allergic. This reaction can
be mild, with only hives and a hoarse voice. Or, at rare times, it can
be more severe, with a quick and serious drop in blood pressure and
problems breathing. Severe anaphylaxis can be fatal. Anaphylaxis
requires emergency medical treatment, medications, and, at times, a
machine to help in breathing. Skin testing just before giving DAT can
show if a person is allergic, and things can be done to lower the risk.

Also, a small number of people (\<5%) getting horse serum may get pains
in their joints and back, fever, and a rash a few weeks after treatment.
These problems can last a couple of weeks. This is called serum
sickness. Rarely, persons with serum sickness can have a more severe
illness with kidney, nerve, or heart inflammation. Doctors can treat
serum sickness with standard medicines.

**ARE THERE RISKS RELATED TO PREGNANCY?**

There are no known extra risks from DAT for a pregnant woman or her
unborn baby (fetus). Because about a third of all patients who have
diphtheria do not survive without DAT, treating diphtheria is of much
greater benefit to the mother or the fetus than the possible risk of DAT
treatment. Facts we learn from this test will be used only to help us
learn if this product has any harmful effects on the mother or fetus.

**WHAT ABOUT PRIVACY?**

The medical records with this protocol are subject to the terms of the
Privacy Act of 1974, 5 U.S.C. Section 552a. People who work for the
local health department, the CDC, and FDA may read your/your child's
medical records. They may obtain personally identifying information from
these records. All data we gather about you/your child will be kept
private to the extent allowed by law. You/your child will not be named
when we present the results.

**IS THIS PROTOCOL VOLUNTARY?**

It is your/your child's choice to receive DAT. You/you child may refuse
or stop treatment at any time. If so, you/your child will not lose the
right to other health care or services that you/your child might be due
apart form this. You/your child are not giving up any of your legal
rights by signing this form. We will give you a copy of this form.

**WHAT ARE THE COSTS?**

CDC is providing DAT to you/your child at no cost. CDC does not pay for
skin tests or lab tests.

Thus, you (or your health insurer, Medicare, or Medicaid) will have to
pay for any care that is needed

**WHAT OTHER CHOICES DO YOU/YOUR CHILD HAVE BESIDES THIS PROTOCOL?**

No other treatment for diphtheria infection exists.

**WHAT HAPPENS IF I OR MY CHILD ARE HARMED?**

If you are or your child is harmed because of receiving DAT, treatment
will not be provided by CDC. CDC does not normally pay for harm done to
you/your child because of receiving DAT treatment. Thus, you (or your
insurer, Medicare, or Medicaid) will have to pay for any care that is
needed. However, by signing this consent form and agreeing to receive
DAT treatment, you are not giving up any of your or your child's rights.

**WHO DO YOU CALL WITH PROBLEMS OR QUESTIONS?**

You can ask your treating physician any question you have about this
treatment. If you/your child have concerns or questions about the DAT
treatment, please call your treating physician at
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ or the
Bacterial Vaccine-Preventable Diseases Branch, National Immunization
Program, CDC at (404) 639-8765.

If you think you or your child have been injured or have questions about
your or your child's rights as a participant in this protocol, please
call CDC\'s Deputy Associate Director for Science at 1-800/584-8814.
Please leave a message including your/your child's name and phone
number, including your area code. Say that you are calling about CDC
Protocol \# 4167. Someone will call you back as soon as possible.

**CONSENT STATEMENT**

> □ I have read and understood the above information or had it read to
> me/my child.
>
> □ I have had my questions answered.
>
> □ I agree to take investigational DAT to treat diphtheria or for my
> child to take DAT to treat diphtheria.
>
> □ I agree to let the local/state health department, CDC, and the FDA
> see my/my child's medical records.
>
> □ I **DO NOT** agree to take investigational DAT to treat diphtheria
> or for my child to take DAT to treat diphtheria.

Signature of patient or
guardian**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

Date
**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

Type/Print name of
patient**\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

**IF PATIENT IS INCAPABLE OF PROVIDING INFORMED CONSENT**

If the patient is too ill to give informed consent; and if next of kin
cannot be found after an effort is made to locate them; and if the
illness is life threatening, a physician has made the decision to begin
this treatment:

Signature of physician:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Date: \_\_\_\_\_\_\_\_\_\_\_

Time of day: \_\_\_\_\_\_\_\_\_\_\_ AM/PM (circle one)

Type/print name of physician:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Efforts to reach the next of kin have included the following (describe):