Download June 2003 presentation to FDA advocates by Nancy Roach, MNCF

SUMMIT ON CANCER CLINICAL TRIALS - V
Dilimmas and Complexities of Compassionate Use
What is Compassionate Access?
• Expanded Access Protocols and Single Patient
Treatment INDs.
• Expectation of Benefit vs. False Hope
• Is There a Conflict with Clinical Trials?
• When Should Compassionate Access Be
Granted and Who Decides?
What is Compassionate Access?
• Expanded Access Protocol – A treatment
regimen for a predefined group of patients
• Single Patient Treatment IND – A treatment plan
for an individual who does not meet the eligibility
requirements of the clinical trial protocol
When is Expanded Access
Appropriate?
• Expanded access protocols should be
based on a realistic possibility of
therapeutic benefit
• Protocol should be designed so that it
does not conflict with Phase III trial
enrollment
When is Single Patient Treatment
Appropriate?
• Experimental agent has not been (and
may never be) tested for efficacy in a
particular patient’s type of cancer or
specific medical condition and the
patient is not eligible for a clinical trial
• Treatment use of an investigational drug
may be the only opportunity for an
extension of life
What is the probability of benefit
from prescription drugs?
• Commonly prescribed drugs have limited
efficacy/response
–
–
–
–
–
ACE-1
beta-blockers
SSRIs
tricyclic AD
statins
10-30%
15-35%
10-25%
20-50%
10-60%
• Significant occurrence of adverse reactions
– 2.1 million people hospitalized annually due to
adverse drug reaction
– Of those, 106,000 end in fatality
What is the probability of benefit
from an experimental cancer drug?
• Unknown in the best of circumstances
• Improbable in the typical context of
compassionate access
• Example: C225 produced a 22% partial
response of ~ 186 day duration
Reasons for Publicity About Treatment
Advances
• Peer-reviewed results are of clinical practice
significance
• Peer-reviewed results are
preliminary/speculative and interesting
• Political agenda (NCI, HHS looking for funding
from Congress
More Reasons for Publicity About
Treatment Advances
• Announcement designed to promote a
product or a company
• Announcement mandated by government for
nonmedical reason (SEC compliance)
• Inadvertent misrepresentation of science by
the press
• Fraud
Optimism About Experimental
Drugs
• With currently approved drugs: Hope is for
high probability of benefit with possibility of
harm; Reality is certainty of harm with
possibility of benefit.
• Is risk – benefit consideration an individual
decision or a group decision?
Notes from ODAC: Reasons to Deny
Compassionate Access
• “Unbridled treatment use of
investigational drugs may interfere with
enrollment in clinical trials to evaluate the
safety and effectiveness of new drugs.”
• “Sponsors and FDA may be concerned
that patients may refuse to enroll in a
randomized trial designed to compare
standard treatment to experimental
treatment if the experimental treatment is
available outside of trials.”
Does Compassionate Access Interfere
With or Complement Clinical Trials?
• Policies regarding eligibility for clinical
trials and compassionate access
• Compassionate access and accelerated
enrollment in pivotal trials
• Insights into broader uses of
experimental drug?
Compassionate Access and
Crossover Design
• A crossover design can speed accrual
• If the experimental agent is a winner,
crossover will not obscure effectiveness
• If the experimental agent is a winner,
compassionate access helps individuals
and adds to understanding safety
Notes from ODAC: Reasons to Deny
Compassionate Access
• “Sponsors may not have sufficient drug
supply to support widespread treatment
use.”
• Investment required to supply a new drug
during trials and after FDA approval
• Fairness in rationing
– No policy
– Lottery
– Sickest patient first
– Most likely to benefit first
Notes from ODAC: Reasons to Deny
Compassionate Access
• “Sponsors may worry that adverse events
from treatment use reported in patients
who have a poor performance will have
an adverse impact on drug development.”
• Are insights into safety resulting from
compassionate access important?
• Policy and “the greater good.”
Treatment Use During Clinical
Research: Is There Conflict?
• Realistic Expectation of Benefit versus
False Hope
• Faster or Slower to Market
• What is Fair and to Whom?
• Who Decides and How?
Thank you
• Questions via e-mail?
• [email protected]