Abrams
Legacy Statement to TPSAC regarding the process for reviewing Modified Risk Tobacco Product Applications (MRTPAs) David B. Abrams, PhD The Schroeder Institute For Tobacco Research And Policy Studies at Legacy The Johns Hopkins Bloomberg School of Public Health Georgetown University Medical Center / Lombardi Comprehensive Cancer Center
FDA-CTP TPSAC Meeting April 30th 2013
P U B L I C H E A LT H S TA N D A R D
To become an MRTP, manufacturers must demonstrate that the product, as actually used, will: Significantly reduce the harm and the risk of
tobacco related disease to individual users; and Benefit the health of the population as a whole,
taking into account both users of tobacco products and persons who do not currently use tobacco products – PATTERNS OF ACTUAL USE BEHAVIOR – uptake, continued use, cessation 2
P O T E N T I A L PAT T E R N S O F T O B A C C O U S E
Combustible use
Never / Former use
Combustible use
Combustible use
Dual use
Dual use
Noncombustible use
Noncombustible use
Former use
Former use
Time 3
I M P O R TA N C E O F I O M R E C O M M E N D AT I O N S O N M R T PA
Scientific evidence needed Phased approach to data collection and approval Types of high quality randomized controlled trials needed to assess exposure reductions at the individual level Delivery of high quality data Conduct of research in subpopulations of interest Good research practices Transparent system of evidence synthesis Public disclosure of data Proper conduct of research Mindful of past Industry behavior (e.g. light, Judge Kessler) 4
L E G A C Y R E C O M M E N D AT I O N S 1.
Craft phased research approach (similar to CDER’s Investigational New Drug (IND) and New Drug Application (NDA) process).
2.
Extend phased approach to address potential population impact of proposed MRTP.
5
PHASED APPROACH The phased approach should include: Laboratory studies Pre-clinical studies Clinical studies - assess reduced harm at the individual level Pre-market population studies - rigorously test for potential impacts at the population level, use of modeling informed by behavior Thresholds of evidence for reduction in harm at the individual level must be met at each phase
6
P R E - M A R K E T P O P U L AT I O N S T U D I E S
Pre-market population studies of potential MRTPs should assess: Actual use behavior: in limited, but representative
subsamples Bio-markers of harm Dual use potential and changes in risk and harm
exposure of dual use or lack thereof Impacts on initiation and progression of tobacco use Delays in cessation of combustible tobacco
7
L E G A C Y R E C O M M E N D AT I O N S 3.
Specify data collection and modeling requirements to develop models that can be used across MRTPs at every phase, to best inform the models to accurately estimate benefits and harms at the population level.
8
U S E S O F C O M M O N M RT PA M O D E L S
Inform the development of thresholds for results at each phase of data collection (e.g., preclinical, clinical, population study) at which a given MRTPA can move forward or be rejected.
Update models throughout the post-market surveillance period to determine when an approved MRTP should be removed from the market.
Permit simultaneous comparison of proposed MRTPs which may inform updates to requirements made by FDA for the MRTPA process.
9
L E G A C Y R E C O M M E N D AT I O N S 4.
Conduct pre-market review and testing of labeling, marketing materials, marketing plans for all MRTPA.
5.
Include pre-market studies assessing the impact of proposed marketing messages on knowledge, attitudes, perceptions, beliefs and actual tobacco use behavior.
10
PRE-MARKET TESTING OF MARKETING Testing
must be done in a range of populations, including vulnerable populations
Testing
of marketing messages in population
studies Focus group testing is insufficient
11
L E G A C Y R E C O M M E N D AT I O N S 6.
Require that MRTPA marketing plans be aligned with the goal of tobacco harm reduction. Contain consumer education to improve public health
– consistent with public statements of Tobacco Industry • Promoting total switching to MRTP • Educating that dual use does not necessarily improve individual or public health and may escalate harm
12
L E G A C Y R E C O M M E N D AT I O N S 7.
Require that ALL marketing, labeling and advertising materials for MRTPs – and not just a sampling – be reviewed and tested by FDA preand post-market.
8.
Build capacity to conduct post-market surveillance of MRTPs in addition to that required of the industry.
13
P O S T- M A R K E T S U RV E I L L A N C E Frequent
assessment during first year following MRTP introduction to the market e.g., At 3, 6, 9 and 12 months
Frequent
updates to MRTP models and parameter estimates to project population impact in the post-market period, based on actual patterns of tobacco use behavior. 14
L E G A C Y R E C O M M E N D AT I O N S 9.
Create Guidance and Regulations for the timely removal of an MRTP or modification of marketing messages should a product prove not to protect public health in the post-market period.
15
T R A N S PA R E N C Y O F T H E P R O C E S S Statue
requires MRTPA process to be transparent
FDA should: Make MRTPAs available to the public as soon as
possible Not create an overbroad standard for “trade secrets” or “confidential information” Allow sufficient comment periods so that interested parties can supply meaningful comments
16
CONCLUSION
Legacy is hopeful given the potential that modified risk products may hold in helping to reduce the death and disease caused by tobacco use.
However, we also believe that strong science must prove reduced risk at both the individual and population levels before such a product can enter and remain in the marketplace.
TPSAC has a critical task in assessing MRTPAs. 17
[email protected]
FDA-CTP TPSAC Meeting April 30th 2013
P U B L I C H E A LT H S TA N D A R D
To become an MRTP, manufacturers must demonstrate that the product, as actually used, will: Significantly reduce the harm and the risk of
tobacco related disease to individual users; and Benefit the health of the population as a whole,
taking into account both users of tobacco products and persons who do not currently use tobacco products – PATTERNS OF ACTUAL USE BEHAVIOR – uptake, continued use, cessation 2
P O T E N T I A L PAT T E R N S O F T O B A C C O U S E
Combustible use
Never / Former use
Combustible use
Combustible use
Dual use
Dual use
Noncombustible use
Noncombustible use
Former use
Former use
Time 3
I M P O R TA N C E O F I O M R E C O M M E N D AT I O N S O N M R T PA
Scientific evidence needed Phased approach to data collection and approval Types of high quality randomized controlled trials needed to assess exposure reductions at the individual level Delivery of high quality data Conduct of research in subpopulations of interest Good research practices Transparent system of evidence synthesis Public disclosure of data Proper conduct of research Mindful of past Industry behavior (e.g. light, Judge Kessler) 4
L E G A C Y R E C O M M E N D AT I O N S 1.
Craft phased research approach (similar to CDER’s Investigational New Drug (IND) and New Drug Application (NDA) process).
2.
Extend phased approach to address potential population impact of proposed MRTP.
5
PHASED APPROACH The phased approach should include: Laboratory studies Pre-clinical studies Clinical studies - assess reduced harm at the individual level Pre-market population studies - rigorously test for potential impacts at the population level, use of modeling informed by behavior Thresholds of evidence for reduction in harm at the individual level must be met at each phase
6
P R E - M A R K E T P O P U L AT I O N S T U D I E S
Pre-market population studies of potential MRTPs should assess: Actual use behavior: in limited, but representative
subsamples Bio-markers of harm Dual use potential and changes in risk and harm
exposure of dual use or lack thereof Impacts on initiation and progression of tobacco use Delays in cessation of combustible tobacco
7
L E G A C Y R E C O M M E N D AT I O N S 3.
Specify data collection and modeling requirements to develop models that can be used across MRTPs at every phase, to best inform the models to accurately estimate benefits and harms at the population level.
8
U S E S O F C O M M O N M RT PA M O D E L S
Inform the development of thresholds for results at each phase of data collection (e.g., preclinical, clinical, population study) at which a given MRTPA can move forward or be rejected.
Update models throughout the post-market surveillance period to determine when an approved MRTP should be removed from the market.
Permit simultaneous comparison of proposed MRTPs which may inform updates to requirements made by FDA for the MRTPA process.
9
L E G A C Y R E C O M M E N D AT I O N S 4.
Conduct pre-market review and testing of labeling, marketing materials, marketing plans for all MRTPA.
5.
Include pre-market studies assessing the impact of proposed marketing messages on knowledge, attitudes, perceptions, beliefs and actual tobacco use behavior.
10
PRE-MARKET TESTING OF MARKETING Testing
must be done in a range of populations, including vulnerable populations
Testing
of marketing messages in population
studies Focus group testing is insufficient
11
L E G A C Y R E C O M M E N D AT I O N S 6.
Require that MRTPA marketing plans be aligned with the goal of tobacco harm reduction. Contain consumer education to improve public health
– consistent with public statements of Tobacco Industry • Promoting total switching to MRTP • Educating that dual use does not necessarily improve individual or public health and may escalate harm
12
L E G A C Y R E C O M M E N D AT I O N S 7.
Require that ALL marketing, labeling and advertising materials for MRTPs – and not just a sampling – be reviewed and tested by FDA preand post-market.
8.
Build capacity to conduct post-market surveillance of MRTPs in addition to that required of the industry.
13
P O S T- M A R K E T S U RV E I L L A N C E Frequent
assessment during first year following MRTP introduction to the market e.g., At 3, 6, 9 and 12 months
Frequent
updates to MRTP models and parameter estimates to project population impact in the post-market period, based on actual patterns of tobacco use behavior. 14
L E G A C Y R E C O M M E N D AT I O N S 9.
Create Guidance and Regulations for the timely removal of an MRTP or modification of marketing messages should a product prove not to protect public health in the post-market period.
15
T R A N S PA R E N C Y O F T H E P R O C E S S Statue
requires MRTPA process to be transparent
FDA should: Make MRTPAs available to the public as soon as
possible Not create an overbroad standard for “trade secrets” or “confidential information” Allow sufficient comment periods so that interested parties can supply meaningful comments
16
CONCLUSION
Legacy is hopeful given the potential that modified risk products may hold in helping to reduce the death and disease caused by tobacco use.
However, we also believe that strong science must prove reduced risk at both the individual and population levels before such a product can enter and remain in the marketplace.
TPSAC has a critical task in assessing MRTPAs. 17
[email protected]
