# Presentation: 340694

## Regulatory Background on Treatment Use of Investigational Drugs for Cancer

- Grant Williams, M.D.
- Deputy Division Director
- DODP/CDER/FDA

## Overview

- Regulatory background
- Issues discussed at December 2000 and June 2001 ODAC meetings

## Definitions

- IND (Investigational New Drug Application)
- Sponsor
- Drug manufacturer
- Investigator

## Investigational Drug Use

- Clinical investigations
- Treatment use

## Treatment Use of Investigational Drugs

- Single-patient use
- Expanded access

## Treatment Use of Investigational Drugs

- Expanded Access
- Well-defined procedures
- Group C
- Treatment IND
- Other expanded access protocols

## Treatment Use of Investigational Drugs

- Single-patient use
- Single-patient IND
- Single-patient exception

## Requirements for Single-Patient Treatment

- Drug supplier and Sponsor
- Qualified investigator
- IRB approval and informed consent
- FDA concurrence

## Evaluating a Request for Treatment Use

- Items to consider:
- Activity and toxicity of drug
- Other treatment options for patient
- Is sponsor pursuing drug development?
- Will treatment use impede drug development?

## When is Single-Patient Use Appropriate?

- Evidence of safety and/or efficacy
- Stage of drug development (Phase I, etc.)
- Results of studies
- Standard therapy

## Industry Concerns

- Limited drug supply
- Competition with regulatory process
- Patient entry
- Shared resources
- Potential to jeopardize safety profile
- Little is learned from single patient use.

## Expanded Access Protocols

- When?
- Promising preliminary results
- Common tumors with few options
- Many requests are anticipated

## Single informed consent form
Equal access, no special cases
Exclude patients eligible for registration studies
Restrict to disease with activity
Negotiate data collection requirements
Consider omitting non-serious and expected AEs

- Equal access, no special cases
- Exclude patients eligible for registration studies
- Restrict to disease with activity
- Negotiate data collection requirements
- Consider omitting non-serious and expected AEs

- Expanded Access ProtocolsRecommendations from Industry Discussant

## Expanded Access DataLimitations

- Most important data to collect:
- 	Adverse events (unexpected and severe)
- Other data are of questionable value
- single-arm study
- less controlled setting
- inexperienced investigators

**Notes:**
Finally, one of the questions Dr. Kenneally asked FDA to address was how these data from expanded access protocols might be used when the company submits a new drug application, and whether these data could decrease the time to NDA submission.  Of course specifics vary from protocol to protocol, but these are some generalizations I would suggest.  
-First, the most important data to collect are those on adverse events, especially serious events and unexpected new toxicities.   
-Other data are probably seldom useful in this setting, that is, with a single-arm study, where conditions vary widelyfrom patient to patient, and where physicians are less experienced at collecting data and may not have the same support staff for assuring high-quality data.  

-Finally, it does not seem likely that expanded access data will speed NDA submission and approval for cancer drugs because usually the rate-limiting step in this process is collection of data on effectiveness-- data that will usually come from the clinical trials.  To speed this process, we need more patients in clinical trials.