As we have alluded to before, the House and Senate have been
considering another tweaking of regulations related to pharma as part of the
broad 21st Century Cures Act (Act).
The House has taken a big step forward by approving on a bi-partisan
basis the Act. Most of the headlines are
focused on the increase in NIH funding, but for pharma people there is a lot of
interesting suggested changes in the regulatory environment. NOTE: this is just the House version, the
Senate will not take up the bill to later this year so we don’t know if any of
these changes will come to pass – so far at least the White House is not
threatening a veto.
You can find the whole bill
here.
Medical Affairs: All
about off label communication
Act Requirement:
Subsection 2102 explicitly requires the regulatory
clarification about acceptable dissemination of off-label information:
Not later than 18 months after the date
of enactment of this Act, the Secretary of Health and Human Services shall
issue draft guidance on facilitating the responsible dissemination of truthful
and non-misleading scientific and medical information not included in the
approved labeling of drugs and devices.
Implication for MA:
While conceivably once this guidance is issued anyone (commercial
and medical) from the company can share off-label information, if the guidelines
are anything like the guidance provided by the FDA in their response to the
Amarin lawsuit which we
discussed here that guidance will explicitly require that the information
be discussed by someone from the company with “… the appropriate background or training to
accurately communicate scientific information.”
So, conservatively interpreting that definition, if this act
passes MA should finally have clear guidelines on how to proactively discuss
off-label information. A BIG win for MA.
Clinical Development
and Medical Affairs: Support for innovation in clinical trials
Act Requirements:
There are a number of requirements that could be clarified
by the Act. I will highlight a few I
think are most impactful.
The first is section 2021 which discusses the use of
biomarkers. It establishes a process
whereby biomedical research consortia can identify and agree upon biomarkers,
then submit those biomarkers to the FDA for their review and approval, and once
approved can be used by industry as surrogate endpoint. Draft guidance on this process is due no
later than 24 months after enactment.
The second is subsection 2061, focused on broader use of adaptive
trial design and Bayesian statistics. The Act requires the FDA to update and
finalize the guidance on adaptive trial design within 18 months and issue draft
guidance on the use of Bayesian statistical models within 48 months. So not exactly pushing the envelope on the
Bayesian timeline for draft guidance.
The next is subsection 2062 deals with the use of “real
world” observational / registry / safety data in the application for additional
indications or to meet post-approval requirements. It requires that a program for the use of
this type of data in these ways be established within 24 months including delineating
when this type of data will be acceptable to the FDA, the standards and methods
needed to be followed when collecting this data. One year after the program is up and running
draft guidance is due and then a year after that final guidance is due.
Implications for CD MA
The implications of the acceptance of biomarkers as
acceptable surrogate endpoints should have huge implications. Currently these endpoints are gathered but are
not relied upon for fear that they will not be acceptable. Knowing in advance that they will be
acceptable to the FDA will allow for much more streamlined data collection
efforts.
Further clarity on adaptive trial design will be helpful but
not earth-shattering. Adaptive trial
design draft guidance already exists so all the act is really doing to pushing
to get it out of the draft phase and finalized which should reduce risk and
make adaptive trial designs more acceptable to less risk-tolerant
organizations. This will hopefully push
into becoming a standard in P2 trials, reducing the need for multiple trials. I’m not really qualified to discuss how the
Bayesian statistical model impact development – if you understand this better
than me please leave a note in the comments.
The “real world” data requirement, assuming it produces
clear definitions from the FDA about the qualities that the data has to have to
be acceptable, could be a dual edged sword.
On the one hand, if they have very high expectations about the quality
and cleanliness of this data in some cases, especially registries, it could
raise the costs. On the other hand,
clear definition of what data will be acceptable for additional indication
applications will allow for the use of this data more broadly and thus more of
these studies to be conducted, which is great overall for pharma.
I am curious to know what you think. Please leave a comment here.
