Biopharmaceutical Report I
BY STEVE USDIN, WASHINGTON EDITOR
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.
“IT IS VERY IMPORTANT TO MAINTAIN AND INCREASE SUPPORT FOR UNDIFFERENTIATED RESEARCH.”
ANONYMOUS NIH INSTITUTE DIRECTOR
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 o ffsets 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.
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.”
ANONYMOUS NIH INSTITUTE DIRECTOR
“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.
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.
-----------COMPANIES AND INSTITUTIONS MENTIONED------------------------------------------------------------------------------------
National Institutes of Health (NIH), Bethesda, Md
U.S. Food and Drug Administration (FDA), Silver Spring, Md.
Unsigned Commentary. “Back to School: Science & austerity.” BioCentury (2012)
Usdin, S. “One more vote.” BioCentury (2016)
SAN CARLOS, CA +1 650-595-5333; Fax: +1 650-595-5589
CHICAGO +1 312-755-0798; Fax: +1 650-595-5589
WASHINGTON, DC +1 202-462-9582; Fax: +1 202-667-2922
UNITED KINGDOM +44 (0)1865-512184; Fax: +1 650-595-5589
Trademarks: BioCentury®; BCIQTM; The BioCentury 100TM; Because Real Intelligence is Hard to FindTM; and The Clear Route to ROITM are trademarks of BioCentury Inc.
Use of Images: Certain Images used in BioCentury Inc.’s Publications, Video Content, Websites, Services, Notices and/or Marketing Materials are licensed from Getty Images (US), Inc. Any such image of a person or object so displayed is being used for illustrative purposes only and any such person or object depicted, if any, is merely a model. For more information see “Use of Images” found under the “About Us” tab on the Homepage at www.biocentury.com.
All information provided through BioCentury Inc.’s Publications, Video and Audio Content, and Websites is gathered from sources that BioCentury believes are reliable; however, BioCentury does not guarantee the accuracy, completeness, or timeliness of such information, makes no warranties regarding such information, and is not responsible for any investment, business, tax or legal decision made or action taken in reliance upon such information.