CANCER LEADERSHIP COUNCIL
CLC comments on FDA plan for
implementation of new benefit and risk assessment process
(May 7, 2013)
May 7, 2013
Leslie Kux
Assistant Commissioner for Policy
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
RE:
FDA-2013-N-0196, Food and Drug Administration Prescription Drug
User Fee Act V Benefit-Risk Plan; Request for Comments
Dear Ms. Kux:
The undersigned cancer patient, provider, and research
organizations appreciate the opportunity to comment on a
structured approach to: 1) the evaluation of benefits and risks
as part of the regulatory decision-making process, and 2) the
communication of the benefit-risk assessment to the
public. We commend the agency for meeting the
aggressive deadlines in the PDUFA Reauthorization Goals and
Procedures Fiscal Years 2013 through 2017 for implementing a
structured benefit-risk assessment process, including standards
for the communication of the assessment to the public.
The Draft PDUFA V Implementation Plan, “Structured Approach to
Benefit-Risk Assessment in Drug Regulatory Decision-Making,”
says that a framework for benefit-risk decision-making that
“summarizes the relevant facts, uncertainties, and key areas of
judgment, and clearly explains how these factors influence a
regulatory decision,” may yield significant advantages.
According to the plan, these include: 1) informing and
clarifying the regulatory discussion, 2) providing transparency
about different regulatory conclusions by different parties
using the same information, 3) communicating to the public the
basis for FDA regulatory decisions, and 4) documenting a
regulatory decision for consideration by the agency when it
considers similar benefit-risk questions in the
future. These are ambitious goals for a structured
benefit-risk assessment, and we will offer below some advice
about how to realize some of these objectives.
Ensuring that Structured Benefit-Risk Assessment Does Not
Compromise Cancer Drug Review
Before identifying strategies to optimize the benefit-risk
assessment process, we would like to note the potential
detrimental effects of this process. As the implementation
plan states, the benefit-risk assessment “should support the
work of review staff throughout the lifecycle of a drug by
capturing the full range of decisions from pre-market review
through any regulatory actions that are necessary in the
post-market setting.” The plan also states that, “a
systematic approach should efficiently integrate into a review
teams’ existing processes and work products.” We urge the
agency to take steps, if it requires the utilization of
the framework document for structured benefit-risk assessment,
to ensure that the document does not require FDA review staff to
undertake a process that is parallel to and duplicative of
review of safety and efficacy data and regulatory
decision-making.
We are concerned that duplication of regulatory activities or
requirements could result in a slowdown in the regulatory review
process. Cancer patients have benefited significantly from
improvements in regulatory review times, and we are concerned
that the structured benefit-risk assessment process could serve
to undermine that progress because review staffers will shoulder
additional responsibilities associated with the structured
assessment.
We also note that there are additional provisions in the Food
and Drug Administration Safety and Innovation Act (FDASIA) that
hold promise of improving the review of cancer therapies, and
the implementation of the benefit-risk assessment process should
not challenge those improvements in regulatory review. The
breakthrough therapy designation, which facilitates greater
communication between sponsor and agency in the review process,
has been identified as a FDASIA authority that may hold special
potential to enhance cancer drug review.
In moving forward with the structured benefit-risk assessment
and other provisions of FDASIA that will improve the regulatory
review process, FDA must meet the standard it has articulated,
which is to integrate these authorities and procedures into
“existing processes and work products.”
Optimizing Structured Benefit-Risk Assessment
The benefit-risk framework document, published on page 7 of the
Implementation Plan, has the potential to provide a solid
summary of the agency’s rationale for regulatory action.
Two decision factors in the document – analysis of condition and
current treatment options -- will prompt the agency to identify
“evidence and uncertainties” related to those factors that are
critical to the informed evaluation of cancer
therapies. We believe that the information
related to current treatment options will identify the impact of
those treatments on the quality of life of patients, including
but not limited to the side effects of treatment and the
potential late and long-term effects of treatment. This
information provides important context for review of new
treatments and also serves to identify unmet needs, related to
both improved overall survival and quality of life, that
reviewers should consider in the regulatory decision-making
process. We also recommend, as the framework document is
put into routine use, that the analysis of the condition be
updated when a new therapy for that condition is
evaluated. As knowledge about cancer types,
cancer subtypes, and molecular diagnosis deepens, that knowledge
should be reflected in the benefit-risk framework document and
in regulatory review.
We also believe that the public and FDA review teams will
benefit from the evaluation of risk management that the
framework document requires as well as from the subsequent
publication of that evaluation. It is often suggested that
cancer patients have an exceptionally high tolerance for
treatment side effects. As patients with some cancer
diagnoses find that they have a range of treatment options, they
may desire more information about the risks associated with all
options and also a consideration of risks of approved therapies
in the regulatory review of new drugs. There is promise
that the framework document will encourage more rigorous
evaluation of risk management strategies of new and already
approved drugs and over time encourage comparison of the risk
management strategies of different drugs.
Characterizing Uncertainty in Benefits and Risks
We commend the decision of FDA regarding the manner in which it
will utilize the benefit-risk assessment in FY 2013. The
agency indicates that it will focus on: 1) uncertainty about the
benefit-risk assessment that is based on pre-market clinical
trial data from trials that exclude patients with chronic
conditions, who are over a certain age, or who do not meet other
enrollment criteria but may be treated with the drug after
approval and 2) uncertainty about the meaning of post-market
safety signals that may emerge from a wide range of sources and
that not be consistent with safety signals from trials.
This use of the benefit-risk assessment framework may over time
inform the regulatory review process, including the review of
cancer drugs, and at the same time provide patients and the
public a greater understanding of uncertainties that arise in
the review process.
Five-Year Plan
FDA has indicated that it will adhere to a five-year plan,
revising and refining the benefit-risk assessment process as
necessary. FDASIA anticipates a five-year process, and we
believe that a constant process of refinement of the
benefit-risk assessment tool and its utilization will be
necessary. There are many unknowns about how the
benefit-risk framework will be used and how it will affect the
speed and efficiency of the regulatory review process, and a
rigorous evaluation process is needed to ensure that the
framework assists FDA and is in the best interest of the
patients who rely on FDA-regulated therapies.
Sincerely,
Cancer Leadership Council
Bladder Cancer Advocacy Network
International Myeloma Foundation
The Leukemia & Lymphoma Society
LIVESTRONG Foundation
Lymphoma Research Foundation
National Coalition for Cancer Survivorship
National Lung Cancer Partnership
Ovarian Cancer National Alliance
Pancreatic Cancer Action Network
Prevent Cancer Foundation
Susan G. Komen for the Cure Advocacy Alliance
Us TOO International Prostate Cancer Education and Support
Network