SUMMIT ON CANCER CLINICAL TRIALS - VDilimmas 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 10-30%– beta-blockers 15-35%– SSRIs10-25%– tricyclic AD 20-50%– statins 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?

• bob.erwin@lsbc.com