The Co-Directors of the Center for Management
Research in Healthcare at Vanderbilt,
David Dilts and Alan Sandler, reported a study
of an alarming nature to the National Cancer
Institute (NCI). The study was covered by The
Cancer Letter and documented that cancer
trials take an average of 800 days to start. The
clinical trials program in the US is broken and
apparently nobody has noticed: 800 days! Can
you imagine that? The response of the NCI
Director was a vow to cut the time to approval
in half. At 400 days the system would still be
broken. Dilts and Sandler reported that for
cooperative-group studies, a protocol takes
800 days from conception to activation, with an
additional 200 days at a cancer center. Even
an investigator-initiated trial at a cancer center
takes a median of 116 to 252 days, and if you
make amendments to a study it goes back
to the end of the line. Furthermore, the study
by Dilts and Sandler was conducted by two
cooperative groups at four centers selected
by NCI because they scored better than most
(in peer review) on the function of their clinical
trials programs. The solutions offered by
the authors of the study to rectify this situation
were not of much help (e.g. start fewer studies,
stop tweaking studies).
We live in an age where we are blessed with
bounteous information about critical steps
in the pathways that cancer cells use to outstrip
the growth of normal cells and information
about how their cell-death pathways are
broken. Although we have the specific agents
and the opportunity to capitalize on the whole
concept of ‘targeted therapy’ we find ourselves
unable to use these advances. If one looks
at past successes in treatment, they were
characterized
by the ability to test an idea
rapidly, and to tweak studies to allow swift
adjustment of protocols in response to events
happening in real time. I have not examined
the protocols in question directly, but I would
not hesitate to suggest that a study that takes
800 days to activate is hopelessly outdated
the day it starts. Furthermore, if investigators
are encouraged to avoid tweaking, then the
talents of our best investigators are either not
being used or are being wasted.
At my own institution I reside on many committees
involved in protocol review, and I can
say with authority that we are hopelessly
over-regulated.
Although cancer centers are
not perfect and have many problems of their
own, they are still where the knowledge base
is. The requisite talent to know the right way
to design and modify an ongoing study does
not reside on remote review committees at the
NCI or the FDA, yet those are the places where
the delays are greatest. Too many cooks are
spoiling the broth.
A step towards fixing this problem would
be to delegate the entire review and approval
process, at least for phase I and II studies,
to NCI-designated cancer centers with NCIapproved
clinical trials programs, with the NCI
and FDA only retaining audit responsibilities.
This was the role envisioned for cancer centers
by those who framed the NCI Act of 1971.
Most of these regulations have been imposed
on us by the US congress in the name of
patients’ safety. Review boards set up and
codified in regulations to protect patients are
doing just the opposite. They prevent patients
from having access to the fruits of the war on
cancer and the best we have to offer.