1. SUMMIT ON CANCER CLINICAL TRIALS - V
Dilimmas and Complexities of Compassionate Use

2. 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?

3. 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

4. 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

5. 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

6. What is the probability of benefit from prescription drugs?
Commonly prescribed drugs have limited efficacy/response
ACE %
beta-blockers %
SSRIs %
tricyclic AD %
statins %
Significant occurrence of adverse reactions
2.1 million people hospitalized annually due to adverse drug reaction
Of those, 106,000 end in fatality

7. 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

8. 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

9. 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

10. 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?

11. 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.”

12. 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?

13. 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

14. 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

15. 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.”

16. 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?

17. Thank you
Questions via ?