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How politics trumped peer review at Texas cancer institute
Charles Sherr is one of nearly three dozen scientists who recently resigned
from a publicly financed $3bn effort to spur innovative cancer research. In
this personal view, he explains why
The Cancer Prevention and Research Institute of Texas (CPRIT), established
by a constitutional amendment approved by Texas voters, authorized $3
billion over 10 years “to fund groundbreaking cancer research and
prevention” (www.cprit.state.tx.us/about-cprit). A two tiered peer review
group organized by chief scientific officer Al Gilman, a Nobel prize winner,
included a council of seven members (chaired by an eighth member, Nobel
winner Phil Sharp). CPRIT council members led committees that collectively
included more than 100 expert cancer biologists, medical scientists, and
physicians (all from institutions outside Texas) who were charged with
reviewing proposals from Texas investigators.
The council and committee members critiqued a broad spectrum of applications
, including individual investigator awards, multiple investigator awards,
translational (bench to bedside) initiatives, training grants, pre-clinical
and clinical trials, and high risk, early stage drug discovery. Reviewers
were urged to apply only a single standard: does the application propose “
groundbreaking” research likely to transform our understanding of cancer.
In enlisting expert reviewers and leading one such committee (as a non-
voting member), I was personally energized by the efforts of my 16 panelists
who, without prejudice or conflict of interest, rigorously scrutinized and
recommended only the best of the best proposals for funding. All
applications under consideration were refereed by at least three panel
members, who individually submitted critiques and merit scores that were
later made available to the entire committee.
At meetings held twice yearly in Dallas, assembled panelists discussed
potentially meritorious applications and voted priority scores, which were
used as the basis for recommending funding. Gilman attended these meetings
to provide procedural advice but did not participate in the review process
or influence my committee’s deliberations. Aside from the grant review
process, council members convened by video conferencing at least once a
month to consider ancillary CPRIT funding for investigators who were being
recruited to various Texas institutions. Medical scientists who participated
in these processes frequently commented “this has been the best peer
review experience of my career.” I felt that way myself.
In the spring of 2012, there was a sea change. First, council members became
aware that certain members of the CPRIT Oversight Committee, which includes
nine citizens appointed by the governor, lieutenant governor, and speaker
of the house, plus two additional representatives of the attorney general’s
and comptroller’s offices, had accused Gilman of directing funds to his
previous parent organization, the University of Texas Southwestern Medical
Center in Dallas. Some members of the oversight group expressed
disappointment that CPRIT funds had not been equally distributed to
institutions in their geographical areas, acting in this respect like
congressmen who direct “pork” to their districts.
CPRIT also accepted a 6.5 page proposal to fund the Institute for Applied
Cancer Science (IACS) at the MD Anderson Cancer Center in Houston. This
proposal, described as “commercialization” and requesting $18m (￡11m,
4m) for first year operations, was not submitted via the required route or
format. The existence of the IACS was not revealed to Gilman or to the
Research Review Council, despite its goal: early stage drug development. The
brief document mentions no specific drug targets, no lead compounds, no
intellectual property, and alludes only vaguely to company based technology
development.
The IACS proposal was approved within three weeks of its receipt by the
overseers after review by a commercialization panel but without
consideration by any members of the established CPRIT research review panels
. Given this expenditure, overseers shelved funding of a slate of multiple
investigator awards that had been recommended highly by the CPRIT review
committees. Gilman’s position, and that of the council, was that the IACS
proposal should be resubmitted as a detailed document and subjected to
scientific review. In a letter to the overseers, the Council wrote: “The
failure to include us in the process calls into question our roles and the
integrity of the review program in general. More importantly, this bypass is
inherently unfair to every scientist in Texas who participates in the CPRIT
program.” Yet, the decision of the overseers that “commercialization
incubators” need not be subjected to equal scrutiny triggered Gilman’s
announced October departure. Following an ongoing round of grant reviews
completed in September, Gilman and CPRIT council members tendered their
resignations. All 16 members of my review committee resigned in the
following weeks.
In an email inadvertently copied to a member of a CPRIT research review
panel, the chairman of the oversight committee, James Mansour, said, “
Better to get them all out of the way now. Gives us the prime opportunity to
announce a new regime … The headline at the (upcoming) conference will
automatically migrate to the new direction for research. Gilman and Sharp
and the other resignations will not dominate our conference … Gilman is
gone and so is his influence. There will be a number of Texas Institutions
who will be ecstatic …We need to take advantage of this opportunity to put
a stake in the heart of the past news.”1 In a letter to Mansour, the Texas
governor, lieutenant governor, and house speaker state that “It is now time
for CPRIT to take further steps to fulfill its statutory mission and
expedite innovation that will deliver new cancer treatments to patients
within three to five years” 2.
CPRIT now proposes to spend substantially more of its monies on
commercialization—perhaps as much as half. To date, CPRIT has funded all
company awards that have been recommended by both commercialization and
research reviewers with a substantially smaller fraction of available funds.
As Gilman and Sharp opined: “Texans deserve to hear the truth about cancer
. They must understand that miracles will not happen in a short time.
Progress will not be made by those who simply proclaim without explanation
that they can do better than hundreds of skillfully staffed and well-
financed pharmaceutical and biotechnology companies.” 3 My former CPRIT
colleagues and I agree.
Charles Sherr is one of nearly three dozen scientists who recently resigned
from a publicly financed $3bn effort to spur innovative cancer research. In
this personal view, he explains why
The Cancer Prevention and Research Institute of Texas (CPRIT), established
by a constitutional amendment approved by Texas voters, authorized $3
billion over 10 years “to fund groundbreaking cancer research and
prevention” (www.cprit.state.tx.us/about-cprit). A two tiered peer review
group organized by chief scientific officer Al Gilman, a Nobel prize winner,
included a council of seven members (chaired by an eighth member, Nobel
winner Phil Sharp). CPRIT council members led committees that collectively
included more than 100 expert cancer biologists, medical scientists, and
physicians (all from institutions outside Texas) who were charged with
reviewing proposals from Texas investigators.
The council and committee members critiqued a broad spectrum of applications
, including individual investigator awards, multiple investigator awards,
translational (bench to bedside) initiatives, training grants, pre-clinical
and clinical trials, and high risk, early stage drug discovery. Reviewers
were urged to apply only a single standard: does the application propose “
groundbreaking” research likely to transform our understanding of cancer.
In enlisting expert reviewers and leading one such committee (as a non-
voting member), I was personally energized by the efforts of my 16 panelists
who, without prejudice or conflict of interest, rigorously scrutinized and
recommended only the best of the best proposals for funding. All
applications under consideration were refereed by at least three panel
members, who individually submitted critiques and merit scores that were
later made available to the entire committee.
At meetings held twice yearly in Dallas, assembled panelists discussed
potentially meritorious applications and voted priority scores, which were
used as the basis for recommending funding. Gilman attended these meetings
to provide procedural advice but did not participate in the review process
or influence my committee’s deliberations. Aside from the grant review
process, council members convened by video conferencing at least once a
month to consider ancillary CPRIT funding for investigators who were being
recruited to various Texas institutions. Medical scientists who participated
in these processes frequently commented “this has been the best peer
review experience of my career.” I felt that way myself.
In the spring of 2012, there was a sea change. First, council members became
aware that certain members of the CPRIT Oversight Committee, which includes
nine citizens appointed by the governor, lieutenant governor, and speaker
of the house, plus two additional representatives of the attorney general’s
and comptroller’s offices, had accused Gilman of directing funds to his
previous parent organization, the University of Texas Southwestern Medical
Center in Dallas. Some members of the oversight group expressed
disappointment that CPRIT funds had not been equally distributed to
institutions in their geographical areas, acting in this respect like
congressmen who direct “pork” to their districts.
CPRIT also accepted a 6.5 page proposal to fund the Institute for Applied
Cancer Science (IACS) at the MD Anderson Cancer Center in Houston. This
proposal, described as “commercialization” and requesting $18m (￡11m,
4m) for first year operations, was not submitted via the required route or
format. The existence of the IACS was not revealed to Gilman or to the
Research Review Council, despite its goal: early stage drug development. The
brief document mentions no specific drug targets, no lead compounds, no
intellectual property, and alludes only vaguely to company based technology
development.
The IACS proposal was approved within three weeks of its receipt by the
overseers after review by a commercialization panel but without
consideration by any members of the established CPRIT research review panels
. Given this expenditure, overseers shelved funding of a slate of multiple
investigator awards that had been recommended highly by the CPRIT review
committees. Gilman’s position, and that of the council, was that the IACS
proposal should be resubmitted as a detailed document and subjected to
scientific review. In a letter to the overseers, the Council wrote: “The
failure to include us in the process calls into question our roles and the
integrity of the review program in general. More importantly, this bypass is
inherently unfair to every scientist in Texas who participates in the CPRIT
program.” Yet, the decision of the overseers that “commercialization
incubators” need not be subjected to equal scrutiny triggered Gilman’s
announced October departure. Following an ongoing round of grant reviews
completed in September, Gilman and CPRIT council members tendered their
resignations. All 16 members of my review committee resigned in the
following weeks.
In an email inadvertently copied to a member of a CPRIT research review
panel, the chairman of the oversight committee, James Mansour, said, “
Better to get them all out of the way now. Gives us the prime opportunity to
announce a new regime … The headline at the (upcoming) conference will
automatically migrate to the new direction for research. Gilman and Sharp
and the other resignations will not dominate our conference … Gilman is
gone and so is his influence. There will be a number of Texas Institutions
who will be ecstatic …We need to take advantage of this opportunity to put
a stake in the heart of the past news.”1 In a letter to Mansour, the Texas
governor, lieutenant governor, and house speaker state that “It is now time
for CPRIT to take further steps to fulfill its statutory mission and
expedite innovation that will deliver new cancer treatments to patients
within three to five years” 2.
CPRIT now proposes to spend substantially more of its monies on
commercialization—perhaps as much as half. To date, CPRIT has funded all
company awards that have been recommended by both commercialization and
research reviewers with a substantially smaller fraction of available funds.
As Gilman and Sharp opined: “Texans deserve to hear the truth about cancer
. They must understand that miracles will not happen in a short time.
Progress will not be made by those who simply proclaim without explanation
that they can do better than hundreds of skillfully staffed and well-
financed pharmaceutical and biotechnology companies.” 3 My former CPRIT
colleagues and I agree.
