Patient Access to

Investigational Drugs
 Introduction
• While enrolling subjects into a well
controlled clinical study, it is certain that
some patients, although they have the
disease or condition being studied, will
have to excluded from the study in
compliance with certain criteria defined in
the protocol
• Exclusion may be due to number of
reasons
 Questions…
• What happens when patients are excluded
from clinical study of investigational drugs
& no clinical management technique is
known to be effective or no other
marketed drug is available to treat the
disease or condition?
 Questions…
• What if the patient has already failed to
response to available marketed drugs for
the disease or condition?
• If an investigational drug exists that may
provide necessary relief to the patient by
reducing or curing the symptoms of the
disease or that may provide hope of
increasing the life of the patient, is it
unethical to refuse or withhold treatment to
the patient?
Expanding Patient Access
• Issues
– It would be imperative for a physician to recognize the
need for treatment with the investigational drug
– The physician would have to be willing to accept the
responsibility of using an investigational drug &
monitoring the patient at closer & more controlled
intervals than might be necessary with marketed
drugs
– To avoid compromising the scientific study of the
safety & effectiveness of the investigational drugs
through well planned, well controlled clinical studies,
the patient must be deemed ineligible for all ongoing
clinical studies with the drug
 Result
• Compassionate use exception, granted
upon documented justification, for
investigational drugs to be used to treat an
individual patient
• By identifying an individual patient’s need,
contacting a drug company to confirm
availability of the drug & submitting a case
study & other documents to & receiving
approval from FDA & IRB, the physician
could treat the patient with the
investigational drug
 Result
• Recognizing that the process was
cumbersome and significantly time
consuming & realizing that the patient
access to promising therapies could be
expanded without compromising the
development program of the product, the
FDA changed the law to provide for the
use of investigational drugs in the
treatment of an individual patient or small
group of patients in a managed way.
 3 mech. For treating patients
• Single patient use protocol
– Can be by the investigator in the form of IND
to FDA to treatment between one & five
patients
– Additional patients may be added to the
protocol by filing an amendment to the IND
 3 mech. For treating patients
• Treatment protocol
– Submitted by the study drug sponsor to provide
broader access to an investigational product before
receiving approval from FDA to market the product
– Allows for the treatment of tens to hundreds of
patients under the care of any interested physicians
who wish to treat patients with the product
– Physicians gain participation in the protocol by
contacting the study drug sponsor & completing a
small number of regulatory documents
– The necessary documents are then filed by the study
drug sponsor as an amendment to their IND
 3 mech. For treating patients
• Emergency Use
– When no other alternative exists
– If the subject has to be provided with the IP drug
( within 30 days), then he may request the
investigational drug from the study drug company &
may treat the patient with the drug if the full conditions
are met
• Pt condition is severe or life threatening
• No other treatment option exists for the patient
• Delay in treatment with the investigational drug could be fatal
to the patient
• There is no sufficient time to prepare & submit to the FDA the
necessary documents for a single patient use protocol
• Notification is provided to the FDA by rapid communication,
indicating the urgency of the request
Cont’d…
• IRB is notified & provides approval
• Within 1 week, the investigator must file
documentation to the FDA along with all
completed regulatory forms.
 Regulatory & legal issues
• For the expanded use protocol to be
justified, sufficient information regarding
the efficacy & short term safety of the drug
should already have been established.
• These protocols are generally limited to
the diseases that are life threatening or
severely debilitating & to patients who
have no alternative therapy
 Legal issues
• Can a patient sue the FDA or the drug
company for access to an investigational
or nonmarketed drug
• Once given access, can the patient sue
the investigator, the drug company or the
FDA for damages sustained while taking
the drug under expanded use protocols
 Legal issues

•YES
 Legal issues
• The patient has the right to sue or to
pursue other available avenues to
demand access to a drug that he believes
he needs
• The patient does not give up any legal
rights at any time before, during or after
participation in a typical or expanded use
clinical study & therefore may seek legal
remedy to any damages he alleges
 Legal issues
• The company may be liable in cases
where physicians enter inappropriate
patients under an expanded use protocol
 Regulatory issues
• Drug Availability
– Availability may lag far behind demand for the
drug & this factor can temper the motivation of
the FDA to approve its use.
– Lack of supply poses a difficult problem
– If a protocol is employed a decision must be
made to determine how patients will be
selected, because insufficient supply exists for
all patients with the disease or condition
 Regulatory issues
• Paperwork, Monitoring & control
Responsibility
– Regulatory benefits
– Expanded use studies are required to be
carried out under the supervision of the
sponsor’s IND
– This results in monitoring study conduct &
verifying, tabulating & reporting the data to the
FDA with study drug sponsor
– FDA maintains direct responsibility for the
emergency use protocols & single patient use
protocols submitted by investigators
 Package insert
• By employing the expanded use protocol,
which would include broader patient
populations & variations of the indication,
the sponsor may gain more liberal labeling
from the increased exposure
• Side effects & drug interactions observed
during the expanded use study are
required to be included in the package
insert
 Advantages & disadvantages for
the patient
• Expanded use protocol is generally designed to
circumvent the strict criteria & to provide select patients
with therapeutic advantage not otherwise available to
them
• Patients enrolling in expanded use studies typically do
not qualify for any of the controlled studies with the drug
• Often instituted during the late phase I or early phase II
before the toxic effects are adequately characterized &
certainly before efficacy is demonstrated.
• By extending the patient population outside the
boundaries defined in the original protocol, the statistical
likelihood of side effects increases, as does the potential
that a side effect will present itself that can lead to a new
indication or formulation of the drug
 Advantages & disadvantages for
the sponsor
• To be cost effective for the sponsor, little
or no funding should be expended for
patient expense reimbursement or for
investigators who desire to prescribe the
investigational drug to their patients
• Sponsor shld provide clinical trial material,
recording instruments, medical & scientific
& monitoring expertise to conduct the trials
in accordance with the expanded use
protocol & current FDA regulations &
guidelines.
 Advantages & disadvantages for
the sponsor
• Marketing issues
– Expanded use protocol is good selling tool
– It allows the physician to become familiar with
the drug before its actual marketing
– Opportunity for overly enthusiastic drug
representatives to try to sell the physician on
the drug before FDA approval to market the
drug
– Charging for the drug under an expanded use
program requires prior approval, by the FDA.
 Advantages & disadvantages for
the sponsor
• Ethical & Practical Issues
– Difficulties in informed consent
• Clinical data not available & patients often
desperate for therapy
• If the drug demonstrates efficacy in an individual is
it ethical & practical to continue that patient on the
test drug without the benefit of accurate data?
• Limiting participation in the expanded use protocol
to those patients who have participated in previous
studies with the drug is an additional consideration
for the sponsor
 Advantages & disadvantages for
the sponsor
• Ethical & Practical Issues
– Clinical Trial Supply
• Limited by what the sponsor is able to produce &
using the drug in an expanded use protocol places
a great strain on the supply available for
conducting controlled trials
• Companies often question the risk versus benefits
of providing high cost, long term drug in an
expanded use protocol to patients who ultimately
provide little or no helpful study data while
potentially excluding patients from the controlled
studies
 Advantages & disadvantages for
the sponsor
• Monitoring
– Can be especially tenuous under these
protocols & the data obtained can often be
difficult to interpret
 Study Data from the expanded
use
• Provides an opportunity for obtaining long
term data not captured in the shorter &
more expensive efficacy & safety data
• Side effects can also reveal themselves
that could lead to a new indication for the
compd or odification of its use.
• Safety data management program to be
set up
 Conclusion
• The expanded use protocol when initiated with
careful scientific thought & appropriately
managed can be an extremely tool for obtaining
cost effective information for the FDA,
communities & patient
• It is the responsibility of the investigator, the
sponsor & the FDA to maintain a collaborative
environment so that these studies can serve a
patient population in need of the drug before its
approval & marketing