While the FDA reform provisions in the 21st
Century Cures Act give the agency backing to carefully advance some of its
long-term objectives, an analysis of the bill’s details suggests that when it
comes to NIH, at best the legislation is a missed opportunity to make
meaningful changes at the world’s largest biomedical funding agency, leaving
long-term problems untouched.
At worst, Cures will be a step backward that
will politicize research and skew grant-making toward flashy, short-term
translational science projects that are not designed to fill the knowledge gaps
that prevent biopharma companies from developing scientific advances into new
medicines.
Cures was propelled through Congress by
passionate support for boosting NIH funding in the belief that more money will
quickly lead to medical breakthroughs. In fact, the addition of $ 4.8 billion
over a decade is unlikely to yield quick dividends.
Increased funding for NIH was the Democrats’
price for supporting Cures legislation.
The version of the bill passed by the House of
Representatives in 2015 would have created an $ 8.75 billion “Innovation Fund.”
The fund would have included a $ 2.5 billion Accelerating Advancement Program
that the NIH director could invest in conjunction with institute directors
based on their assessments of scientific opportunities.
The bill was revamped this summer, however,
after Congress allocated the budget offsets that were the basis for mandatory
funding to other priorities, fiscal hawks became queasy over the scale of the
financial commitment, and Democrats came to fear that Cures was their last
chance to boost NIH’s budget ahead of an era of fiscal austerity.
The result was a bipartisan agreement to cut
the NIH funding increase in half and eliminate provisions negotiated by House
Energy & Commerce Committee Chair Fred Upton (R-Mich.) that would have made
the funding mandatory.
Supporters of the act say it will create a
binding commitment for Congress to appropriate the specified funding, but congressional
appropriators could renege on the promises.
The Accelerating Advancement Program has been
scrapped, and almost all the new money will be directed to three big
translational science projects: The Precision Medicine ($1.5 billion), Brain
Research Through Advancing Innovative Neurotechnologies (BRAIN) ($1.5 billion)
and Cancer Moonshot ($1.8 billion) initiatives.
This highly targeted funding will do little to
change the low success rates of grant applications that define the lives of the
vast majority of academic biomedical researchers.
In FY16, 19% of research project grants were
funded, and NIH expects the success rate to fall to 17.5% this fiscal year.
Low success rates foster a climate of
risk-aversion and cronyism at NIH as peer reviewers favor applications that are
most likely to succeed and prefer those submitted by investigators with proven
track records.
The average age of the first NIH R01 grant,
the most common type of research grant, has been stuck at 42 for seven years.
At the same time, the U.S.’s scientific workforce is graying. The number of
NIH-funded researchers over 65 is double the number under 37.
A “capstone” program that was intended to ease
aged researchers off the bench and into retirement was included in the original
House-passed Cures bill but eliminated in the final version.
Cures will establish a Next Generation of
Researchers Initiative, which consists of vague instructions to promote and
prioritize policies that seek to increase opportunities for young researchers.
There is no money or policy mandate attached to the initiative.
LESS CURIOUS
Earmarking funding for specific projects while
inflation erodes the spending power of flat funding for the vast majority of
science that falls outside those projects is not in the best interests of
American science, according to two NIH institute directors who asked not to be
named.
In recent years, even when total NIH funding
has increased, new money has been earmarked for specific translational
projects, they noted, so money available for curiosity-driven scientific
research has been flat or has decreased.
“It is very important to maintain and increase
support for undifferentiated research,” one of the directors said. “[NIH
Director Francis] Collins has pushed projects — BRAIN, Precision Medicine,
Moonshot — and Congress and the president have gotten the false impression that
this is the future of science.”
Beyond these marquee projects, translational
science has been “dominating, crowding out undifferentiated science that often
is the basis for the most important breakthroughs,” the director said.
Cures could have scaled back translational
research spending to create room for more basic research, which is far less
expensive. For example, it could have forced NIH to take a hard look at the
many underpowered “pilot” clinical trials it funds, which benefit the careers
of the academic investigators more than the patients who participate or the
medical fields they are intended to advance.
Failing that, the new law could have — but
won’t — improve the efficiency of NIH’s translational research by ensuring it
produces robust, reproducible data that are highly relevant to the needs of
biopharma companies that develop medicines.
The National Center for Advancing
Translational Sciences (NCATS), which has formal policies intended to ensure
that its research is partnered with product developers, will remain an outlier,
physically and culturally separate from NIH’s other institutes and centers.
Cures also will leave unchanged NIH’s system
for paying overhead costs, such as administrators, buildings and facilities,
which can equal 50%. Reforming overhead payment policies and requiring that
universities pay a substantial portion of principal investigators’ salaries,
would have directed more NIH money to science.
While Congress and NIH could theoretically
make these kinds of changes at any time, the tremendous hype surrounding the
Cures bill has persuaded Capitol Hill that, when it comes to biomedical
research, its job is done.
SETTING TERMS
21st Century Cures includes a section titled
“Increasing Accountability at the National Institutes of Health” that will
centralize power in the hands of the NIH director, make it easier for Congress
to point the finger at institute directors if they approve controversial
research, and inject political considerations into funding decisions.
The core provision will change the law to
create renewable five-year terms for directors of each of NIH’s 27 institutes
and centers, except the National Cancer Institute. Like the NIH director, the
NCI director will continue to be appointed by the president and subject to
Senate confirmation.
The clock will start ticking on current
institute and center directors the day President Obama signs the 21st Century
Cures Act into law — scheduled for Tuesday. Whoever is the NIH director five
years from that day will have the power to renew or dismiss these directors.
The law sets no limits on the number of times
a director can be reappointed. Neither does it create any criteria or specify
any procedures for the NIH director to apply when making renewal decisions.
“Institute directors will be afraid to
criticize bad ideas if they come from a presidentially appointed director who
can fire them,” one of the institute directors told BioCentury. “There is no
reason to believe that the president will always appoint great NIH directors.
Some in the past have been impulsive and ideological.”
Given the slow and unpredictable pace of
science, and the fact that new directors will inherit multiyear programs, it
will be very difficult for institute directors to produce obvious results in a
five-year period. This could create incentives for directors to pursue
short-term wins, and to bow to or anticipate the ideological principles and
intellectual preferences of the NIH director.
In addition, decisions about renewing an
institute director’s tenure will often be made by an NIH director who may not
have appointed her.
All of these considerations could diminish the
stature of NIH institute directors from one of the most prestigious positions
in science to way stations for mid-level managers from research universities to
burnish their resumes, according to the leader of a scientific society who did
not wish to be named.
POINTING
FINGERS
Cures also will facilitate a game of
finger-pointing that has been popular in Congress for generations. The game
starts with staffers combing through thousands of grants until they find one
with a funny or unusual name, and then calling it out as a symptom of waste.
Because Cures requires that institute
directors personally “review and make the final decision” on all research
grants, congressional committees now will be able to haul institute directors
to public hearings to justify any grant. This isn’t likely to engender
risk-taking.
This provision, like the governance
provisions, was proposed by Rep. Andy Harris (R-Md.).
In addition to dramatically expanding the NIH
director’s power, Harris has publicly announced his strong interest in
exercising that power by becoming the next NIH director. So far, the Trump
transition team hasn’t divulged its plans for NIH.
Harris, who was an obstetric anesthesiologist
for three decades and an investigator on one NIH grant prior to his election to
Congress, would be a radical departure from tradition. If nominated and
confirmed, he would be the first NIH director since NIH’s predecessor agencies
were created in 1887 who lacked extensive experience as a scientific researcher
or leader of research teams. A member of the Freedom Caucus, he opposes
embryonic stem cell research.
Collins has met with and charmed hundreds of
members of Congress, creating immense goodwill for NIH among politicians who
aren’t noted for their enthusiasm for science or spending. He spent enormous
amounts of time with the architects of Cures, and the legislation was written
with the idea that someone very much like Collins would be running NIH.
The chairs of four congressional committees
and subcommittees with oversight authority over NIH, including Upton, have
written to Trump urging him to retain Collins.