Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Dear Forum-
I would appreciate your thoughts, comments, or links to other resources. Phase 1a, Phase 1b, Phase 2a, Phase 2b are commonly used in Oncology trials but, I have been unable to find a solid definition of either. While I can define a Phase 1 study and a Phase 2 and the requirements for each (including descriptive definitions in CFR) it is difficult to accurately define and identify a Phase 1a or Phase 1b.  How do you differentiate between them?  

Thank you.

I am not aware of a formal regulatory definition, but common best practice is to describe as follows when the development program breaks down the studies in these categories:

1a: single ascending dose in healthy subjects
1b: multiple ascending dose in healthy subjects
2a: dose ranging in patients
2b: proof of concept in patients

Clinicaltrials.gov which defines their study phases based on 21 CFR 312 does not make this distinction.

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Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States
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Original Message:
Sent: 03-Apr-2020 16:53
From: Anonymous Member
Subject: How to best define a Phase 1a vs Phase 1b

This message was posted by a user wishing to remain anonymous

Dear Forum-
I would appreciate your thoughts, comments, or links to other resources. Phase 1a, Phase 1b, Phase 2a, Phase 2b are commonly used in Oncology trials but, I have been unable to find a solid definition of either. While I can define a Phase 1 study and a Phase 2 and the requirements for each (including descriptive definitions in CFR) it is difficult to accurately define and identify a Phase 1a or Phase 1b.  How do you differentiate between them?

Thank you.

Yes, I'm with Glen. Phase 1a involves single dose escalation to determine the Maximum Tolerated Dose (MTD) whereas Phase 1b involves cohort expansion at multiple ascending dose levels to determine the recommended Phase 2 dose, which could differ from MTD based on various types of evaluations such as correlative studies.

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Jo Huang RAC
Assoc Manager - Regulatory Affairs
Irvine CA
United States
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Original Message:
Sent: 03-Apr-2020 16:53
From: Anonymous Member
Subject: How to best define a Phase 1a vs Phase 1b

This message was posted by a user wishing to remain anonymous

Dear Forum-
I would appreciate your thoughts, comments, or links to other resources. Phase 1a, Phase 1b, Phase 2a, Phase 2b are commonly used in Oncology trials but, I have been unable to find a solid definition of either. While I can define a Phase 1 study and a Phase 2 and the requirements for each (including descriptive definitions in CFR) it is difficult to accurately define and identify a Phase 1a or Phase 1b.  How do you differentiate between them?

Thank you.

Hello all,
Agreed with both Glen and Jo. However, I’ve always seen phase 1 as a single study with two parts SAD and MAD for non-oncology studies. sometimes it can be phase 1/2a, which will be three parts; SAD, MAD and dose range finding in targeted patients. There are different ways we can interpret this based on the nature of your investigational product. (i.e., I’ve worked on a molecule where phase 2 was a pivotal study due to life threatening nature of a disease we were targeting and no treatments were available)

Hope this helps.

Best,
Deep Shah

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Deep Shah
Regulatory Affairs CMC, Biologics

Seattle WA
United States
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Original Message:
Sent: 03-Apr-2020
From: Anonymous Member
Subject: How to best define a Phase 1a vs Phase 1b

This message was posted by a user wishing to remain anonymous

Dear Forum-
I would appreciate your thoughts, comments, or links to other resources. Phase 1a, Phase 1b, Phase 2a, Phase 2b are commonly used in Oncology trials but, I have been unable to find a solid definition of either. While I can define a Phase 1 study and a Phase 2 and the requirements for each (including descriptive definitions in CFR) it is difficult to accurately define and identify a Phase 1a or Phase 1b.  How do you differentiate between them?  

Thank you.