Biomarkers and Precision Medicine Community (BPMC)

This message was posted by a user wishing to remain anonymous

I am looking for a template for an exploratory biomarker analysis plan for immunotherapy drug or any large molecule.  We are quite new to this and trying to see how to put one together.  A template or guide would be helpful.

Thank you in advance!

Hello,

Are you doing FDA biomarker qualification program or this analysis is a part of CSR or retrospective clinical study analysis?
For biomarkers analysis plan it's usually listing of biomarkers by treatment, assessment time and patient; summary statistics by treatment and time point if applicable, change from baseline; correlation analysis to treatment and PK exposure if possible.
The analysis would depend on the type of the biomarker and frequency of its assessments. For example blood biomarker can lend themselves to the biomarker profile and PD parameters such as Emax, Emin, AUE (area under effect curve). For the tissue biopsy biomarkers usually it's lucky to have 2 - one pre-treatment and another after. Matched blood samples are usually very useful.
Correlation analysis can involve correlation to time matched PK concentrations, or PK exposure parameters or treatment and can be as simple as Pearson or Spearman correlation analysis, or involve more complex statistics including PK/PD modelling.

The analysis for biomarkers can be described in the Statistical Analysis Plan for the study or in a separate Data analysis plan with similar structure to SAP.
Usually SAP is a propitiatory document and difficult to share but there are few examples including on clinicaltrials.gov site - ProvidedDocs. 
The analysis has to be tailored to your indication and type of biomarkers and other supporting data you have so any example would be just a guide.

FDA biomarker qualification program is a multi-step process and here is a link to FDA site where they have great resources:
Biomarker Qualification Program

U.S. Food and Drug Administration		remove preview
Biomarker Qualification Program To locate a project or a qualified biomarker go to CDER & CBER's DDT Qualification Project Search database Web content is updated for consistency with 21st Century Cures Act! Resources for Biomarker Requestors MISSION The mission of the CDER Biomarker Qualification Program (BQP) is to work with external stakeholders to develop biomarkers as drug development tools. View this on U.S. Food and Drug Administration >

 


------------------------------
Galina Bernstein Ph.D.
Senior Director of Clinical Pharmacology
AzureDelta Consulting
Thornhill ON
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------

Original Message:
Sent: 12-01-2022 14:25
From: Anonymous Member
Subject: Exploratory Biomarker Analysis Plan

This message was posted by a user wishing to remain anonymous

I am looking for a template for an exploratory biomarker analysis plan for immunotherapy drug or any large molecule.  We are quite new to this and trying to see how to put one together.  A template or guide would be helpful.

Thank you in advance!

Thank you, Galina this is very useful.  The analysis will be part of the CSR and also retrospective clinical study analysis.  We removed the BSAP from the main SAS and have a separate document.  I was wondering how to structure it should follow.  But the above guideline are helpful thank you!



Original Message:
Sent: 12-05-2022 10:42
From: Galina Bernstein
Subject: Exploratory Biomarker Analysis Plan

Hello,

Are you doing FDA biomarker qualification program or this analysis is a part of CSR or retrospective clinical study analysis?
For biomarkers analysis plan it's usually listing of biomarkers by treatment, assessment time and patient; summary statistics by treatment and time point if applicable, change from baseline; correlation analysis to treatment and PK exposure if possible.
The analysis would depend on the type of the biomarker and frequency of its assessments. For example blood biomarker can lend themselves to the biomarker profile and PD parameters such as Emax, Emin, AUE (area under effect curve). For the tissue biopsy biomarkers usually it's lucky to have 2 - one pre-treatment and another after. Matched blood samples are usually very useful.
Correlation analysis can involve correlation to time matched PK concentrations, or PK exposure parameters or treatment and can be as simple as Pearson or Spearman correlation analysis, or involve more complex statistics including PK/PD modelling.

The analysis for biomarkers can be described in the Statistical Analysis Plan for the study or in a separate Data analysis plan with similar structure to SAP.
Usually SAP is a propitiatory document and difficult to share but there are few examples including on clinicaltrials.gov site - ProvidedDocs. 
The analysis has to be tailored to your indication and type of biomarkers and other supporting data you have so any example would be just a guide.

FDA biomarker qualification program is a multi-step process and here is a link to FDA site where they have great resources:
Biomarker Qualification Program

U.S. Food and Drug Administration		remove preview
Biomarker Qualification Program To locate a project or a qualified biomarker go to CDER & CBER's DDT Qualification Project Search database Web content is updated for consistency with 21st Century Cures Act! Resources for Biomarker Requestors MISSION The mission of the CDER Biomarker Qualification Program (BQP) is to work with external stakeholders to develop biomarkers as drug development tools. View this on U.S. Food and Drug Administration >

 


------------------------------
Galina Bernstein Ph.D.
Senior Director of Clinical Pharmacology
AzureDelta Consulting
Thornhill ON
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.

Original Message:
Sent: 12-01-2022 14:25
From: Anonymous Member
Subject: Exploratory Biomarker Analysis Plan

This message was posted by a user wishing to remain anonymous

I am looking for a template for an exploratory biomarker analysis plan for immunotherapy drug or any large molecule.  We are quite new to this and trying to see how to put one together.  A template or guide would be helpful.

Thank you in advance!

The Biomarker Qualification Program is a great resource for clinical validation of a biomarker above and beyond the analytical validation. Thank you for referencing it @Galina Bernstein!

I have done supplemental/exploratory statistical analysis plans in a variety of formats, ranging from something that matches the format of the main SAP to a simple word document explaining the intended analysis. The main purpose is to describe the analyses that you are planning to do before you start looking at the data. That way you can demonstrate that you didn't just run things until you got a result you wanted. You can still run additional statistical analyses after the pre-planned, but would need to caveat that.

------------------------------
Joleen White Ph.D.
AAPS 2023 Global Health Community Past Chair
Bioanalytical 101 Course Development
Head of Bioassay Development
Gates Medical Research Institute
Cambridge MA
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------

Original Message:
Sent: 12-06-2022 10:58
From: Faith Griffin
Subject: Exploratory Biomarker Analysis Plan

Thank you, Galina this is very useful.  The analysis will be part of the CSR and also retrospective clinical study analysis.  We removed the BSAP from the main SAS and have a separate document.  I was wondering how to structure it should follow.  But the above guideline are helpful thank you!



Original Message:
Sent: 12-05-2022 10:42
From: Galina Bernstein
Subject: Exploratory Biomarker Analysis Plan

Hello,

Are you doing FDA biomarker qualification program or this analysis is a part of CSR or retrospective clinical study analysis?
For biomarkers analysis plan it's usually listing of biomarkers by treatment, assessment time and patient; summary statistics by treatment and time point if applicable, change from baseline; correlation analysis to treatment and PK exposure if possible.
The analysis would depend on the type of the biomarker and frequency of its assessments. For example blood biomarker can lend themselves to the biomarker profile and PD parameters such as Emax, Emin, AUE (area under effect curve). For the tissue biopsy biomarkers usually it's lucky to have 2 - one pre-treatment and another after. Matched blood samples are usually very useful.
Correlation analysis can involve correlation to time matched PK concentrations, or PK exposure parameters or treatment and can be as simple as Pearson or Spearman correlation analysis, or involve more complex statistics including PK/PD modelling.

The analysis for biomarkers can be described in the Statistical Analysis Plan for the study or in a separate Data analysis plan with similar structure to SAP.
Usually SAP is a propitiatory document and difficult to share but there are few examples including on clinicaltrials.gov site - ProvidedDocs. 
The analysis has to be tailored to your indication and type of biomarkers and other supporting data you have so any example would be just a guide.

FDA biomarker qualification program is a multi-step process and here is a link to FDA site where they have great resources:
Biomarker Qualification Program

U.S. Food and Drug Administration		remove preview
Biomarker Qualification Program To locate a project or a qualified biomarker go to CDER & CBER's DDT Qualification Project Search database Web content is updated for consistency with 21st Century Cures Act! Resources for Biomarker Requestors MISSION The mission of the CDER Biomarker Qualification Program (BQP) is to work with external stakeholders to develop biomarkers as drug development tools. View this on U.S. Food and Drug Administration >

 


------------------------------
Galina Bernstein Ph.D.
Senior Director of Clinical Pharmacology
AzureDelta Consulting
Thornhill ON
[email protected]

Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.

Original Message:
Sent: 12-01-2022 14:25
From: Anonymous Member
Subject: Exploratory Biomarker Analysis Plan

This message was posted by a user wishing to remain anonymous

I am looking for a template for an exploratory biomarker analysis plan for immunotherapy drug or any large molecule.  We are quite new to this and trying to see how to put one together.  A template or guide would be helpful.

Thank you in advance!