Meeting News

NCI director: Basic science, big data among key areas of opportunity

Norman E. Sharpless

CHICAGO — The director of NCI has identified four “areas of particular opportunity” on which he intends to focus during his tenure.

Norman E. “Ned” Sharpless, MD , unveiled those themes — workforce development, basic science, big data and clinical trials — during remarks this afternoon to American Association for Cancer Research Annual Meeting attendees.

“These are not new areas for NCI,” said Sharpless, making his first major address since taking over as the 15th NCI director in October. “However, I believe the time is ripe for a laser-sharp focus on these four areas based on where we are today in terms of developing science and technology, where the mass and heft of the NCI can play a unique role, and where NCI’s resources, convening power and leadership can act as catalysts.”

Sharpless spoke in detail about each priority area:

Workforce development — The effort to ensure a talented and innovative research workforce for the decades ahead arguably is the most important job of NCI, Sharpless said.

“That means making sure that the best and the brightest don’t get discouraged, that researchers continue to work to further science and fuel the discovery of new approaches and technology that will benefit patients,” he said.

The effort will include funding for training for training at all stages of the career path, with an eye toward particular problems for newly independent early-career investigators.

“One of the biggest hurdles for early-stage investigators is obtaining their first R01 — the most common award for investigator-initiated grants,” Sharpless said. “Given the strong support from Congress as demonstrated by the increase they provided to NCI’s 2018 appropriation, we have been provided the resources to decrease this hurdle a bit. Specifically, I am directing our extramural funders to set aside in 2018 a significant amount of additional funding to increase the total number of first R01s given to early-stage investigators by at least 25%.”

In addition, NCI created R37, a new mechanism that will allow early-stage investigators who receive an R01 to be eligible to have their grant transitioned to an R37 award. This would allow for funding to be extended for up to 2 years.

“In other words, a 5-year R01 grant could become a 7-year R37 grant with minimal extra work,” Sharpless said.

NCI also will focus on developing the most appropriate skills for cancer researchers, including training in basic immunology, disparities research, prevention methodology and data science.

Basic science — NCI will renew its commitment to basic science to increase understanding and drive novel approaches and technologies, Sharpless said.

“There are some voices who feel we have done so well in a few cancer areas that this basic biological focus is no longer needed,” Sharpless said. “These people may argue for more and more spending to address a specific type of cancer, arguing the need in one tumor type is greater than others. And I understand this perspective. There can be a sense that the great ship of cancer research is passing one by when progress is made in treating some cancers but not the ones you personally care most about.”

Although NCI has a considerable investment in translational and disease-specific research, it “can’t afford to bypass the basic science step,” Sharpless said.

“An apt quote that is often attributed to Abraham Lincoln goes, ‘Give me 6 hours to chop down a tree, and I will spend the first 4 sharpening my axe.’ We must sharpen our axes and maintain a committed focus on fundamental science, because there is still very much about cancer that remains unknown,” Sharpless said. “[Although] we have made tremendous progress in some cancers, we have to acknowledge that little or no progress has been made in other types. If you most want to see progress in one of these types of cancer, basic science provides hope.”

NCI can help by focusing on investigator-initiated discovery, Sharpless said. The agency intends to provide another $100 million into investigator-initiated science in 2018, the largest increase to the Research Project Grants pool since 2003.

Efforts also must be made to reduce the administrative burden on scientists, Sharpless said.

“We understand that the grant application and management process is grueling, and I also understand that NIH bureaucracy is particularly challenging on young investigators,” he said.

He described longer award periods, both for the Outstanding Investigator Award and R37, an “initial step in the right direction.”

Big data — Strategies must be identified to catalyze technologies — specifically data technology — to add speed and dimension to work within the cancer enterprise, Sharpless said.

“We must move from passive data sharing to data aggregation, establishing linkage and interoperability of diverse, complex data sets to understand cancer care and provide real-world evidence,” he said.

The effort to harness big data requires special attention to the workforce, such as attracting young data scientists into cancer research, Sharpless said. NCI also will strive to link many large data sets it maintains to ensure interoperability, as well as work with its partners that have novel capabilities or rich data sets, he said.

“We need to change our practices to reward and incentivize data sharing and aggregation — for example, by making aggregation possible by smart consenting and good trial design,” Sharpless said. “We have to do this because the costs of not having big data are too great.”

Clinical trials — The final priority area will be “the vexing problem” of clinical trials, Sharpless said.

“The performance of clinical trials has been deeply affected by the fact that cancer is so heterogeneous,” he said. “Gone are the days when the cardiology paradigm of clinical trials reigned and when we enrolled hundreds of patients in a large phase 3 randomized study with slightly different treatment protocols.”

That approach no longer works in the era of precision oncology, he said.

Today, enrollment is poor and 20% of cancer clinical trials for adults due to accrual problems. The costs of clinical trials are “incredibly expensive,” meaning several good ideas do not get tested, and the “skyrocketing” costs of drug development get passed on to patients, Sharpless said.

“NCI can promote better design of clinical trials,” he said. “We have to get rid of unnecessary exclusion criteria and confusing consent forms. We need to adopt central institutional review boards. We need trials with innovative design, to find inactive agents quickly and, thereby, prioritize good drugs for further testing.”

He called the NCI-MATCH trial — in which patients were allocated to one of more than 30 arms based on somatic genetic testing — “a great example of modern trial design.”

So far, the trial has enrolled more than 6,000 patients at 1,100 sites. A similar approach guided the launch of the Pediatric MATCH Trial, which has expanded to 200 U.S. sites and has enrolled patients in eight therapeutic arms so far.

Greater emphasis also must be placed on recruiting patients to clinical trials from the community setting, Sharpless said.

“Lastly, we have to admit that trials done the old way are inefficient,” he said. “Rather than testing one specific variable in a trial by aggregating data at greater scale, we can learn from every patient. This will require thinking about trials differently, seeing drug development through the lens of a health service researcher, and using the tools of big data and data aggregation.”

Sharpless acknowledged the four priority areas he outlined are highly related, but he emphasized that “other areas not explicitly included” in the vision he outlined will not be ignored.

“NCI is responsible for the entire national cancer program, for research and progress that spans the entire research continuum,” Sharpless said. “We will remain committed to that mission. ...

“We have already made tremendous progress since [the] bad old days of limited options and a poor understanding of the biology of cancer,” he added. “I believe, by applying focus in these areas now, we can further accelerate the pace of that progress.” – by Mark Leiser

 

Reference:

Sharpless NE. NCI and the cancer community: Focusing on patients through innovative research. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.

Norman E. Sharpless

CHICAGO — The director of NCI has identified four “areas of particular opportunity” on which he intends to focus during his tenure.

Norman E. “Ned” Sharpless, MD , unveiled those themes — workforce development, basic science, big data and clinical trials — during remarks this afternoon to American Association for Cancer Research Annual Meeting attendees.

“These are not new areas for NCI,” said Sharpless, making his first major address since taking over as the 15th NCI director in October. “However, I believe the time is ripe for a laser-sharp focus on these four areas based on where we are today in terms of developing science and technology, where the mass and heft of the NCI can play a unique role, and where NCI’s resources, convening power and leadership can act as catalysts.”

Sharpless spoke in detail about each priority area:

Workforce development — The effort to ensure a talented and innovative research workforce for the decades ahead arguably is the most important job of NCI, Sharpless said.

“That means making sure that the best and the brightest don’t get discouraged, that researchers continue to work to further science and fuel the discovery of new approaches and technology that will benefit patients,” he said.

The effort will include funding for training for training at all stages of the career path, with an eye toward particular problems for newly independent early-career investigators.

“One of the biggest hurdles for early-stage investigators is obtaining their first R01 — the most common award for investigator-initiated grants,” Sharpless said. “Given the strong support from Congress as demonstrated by the increase they provided to NCI’s 2018 appropriation, we have been provided the resources to decrease this hurdle a bit. Specifically, I am directing our extramural funders to set aside in 2018 a significant amount of additional funding to increase the total number of first R01s given to early-stage investigators by at least 25%.”

In addition, NCI created R37, a new mechanism that will allow early-stage investigators who receive an R01 to be eligible to have their grant transitioned to an R37 award. This would allow for funding to be extended for up to 2 years.

“In other words, a 5-year R01 grant could become a 7-year R37 grant with minimal extra work,” Sharpless said.

NCI also will focus on developing the most appropriate skills for cancer researchers, including training in basic immunology, disparities research, prevention methodology and data science.

PAGE BREAK

Basic science — NCI will renew its commitment to basic science to increase understanding and drive novel approaches and technologies, Sharpless said.

“There are some voices who feel we have done so well in a few cancer areas that this basic biological focus is no longer needed,” Sharpless said. “These people may argue for more and more spending to address a specific type of cancer, arguing the need in one tumor type is greater than others. And I understand this perspective. There can be a sense that the great ship of cancer research is passing one by when progress is made in treating some cancers but not the ones you personally care most about.”

Although NCI has a considerable investment in translational and disease-specific research, it “can’t afford to bypass the basic science step,” Sharpless said.

“An apt quote that is often attributed to Abraham Lincoln goes, ‘Give me 6 hours to chop down a tree, and I will spend the first 4 sharpening my axe.’ We must sharpen our axes and maintain a committed focus on fundamental science, because there is still very much about cancer that remains unknown,” Sharpless said. “[Although] we have made tremendous progress in some cancers, we have to acknowledge that little or no progress has been made in other types. If you most want to see progress in one of these types of cancer, basic science provides hope.”

NCI can help by focusing on investigator-initiated discovery, Sharpless said. The agency intends to provide another $100 million into investigator-initiated science in 2018, the largest increase to the Research Project Grants pool since 2003.

Efforts also must be made to reduce the administrative burden on scientists, Sharpless said.

“We understand that the grant application and management process is grueling, and I also understand that NIH bureaucracy is particularly challenging on young investigators,” he said.

He described longer award periods, both for the Outstanding Investigator Award and R37, an “initial step in the right direction.”

Big data — Strategies must be identified to catalyze technologies — specifically data technology — to add speed and dimension to work within the cancer enterprise, Sharpless said.

“We must move from passive data sharing to data aggregation, establishing linkage and interoperability of diverse, complex data sets to understand cancer care and provide real-world evidence,” he said.

The effort to harness big data requires special attention to the workforce, such as attracting young data scientists into cancer research, Sharpless said. NCI also will strive to link many large data sets it maintains to ensure interoperability, as well as work with its partners that have novel capabilities or rich data sets, he said.

PAGE BREAK

“We need to change our practices to reward and incentivize data sharing and aggregation — for example, by making aggregation possible by smart consenting and good trial design,” Sharpless said. “We have to do this because the costs of not having big data are too great.”

Clinical trials — The final priority area will be “the vexing problem” of clinical trials, Sharpless said.

“The performance of clinical trials has been deeply affected by the fact that cancer is so heterogeneous,” he said. “Gone are the days when the cardiology paradigm of clinical trials reigned and when we enrolled hundreds of patients in a large phase 3 randomized study with slightly different treatment protocols.”

That approach no longer works in the era of precision oncology, he said.

Today, enrollment is poor and 20% of cancer clinical trials for adults due to accrual problems. The costs of clinical trials are “incredibly expensive,” meaning several good ideas do not get tested, and the “skyrocketing” costs of drug development get passed on to patients, Sharpless said.

“NCI can promote better design of clinical trials,” he said. “We have to get rid of unnecessary exclusion criteria and confusing consent forms. We need to adopt central institutional review boards. We need trials with innovative design, to find inactive agents quickly and, thereby, prioritize good drugs for further testing.”

He called the NCI-MATCH trial — in which patients were allocated to one of more than 30 arms based on somatic genetic testing — “a great example of modern trial design.”

So far, the trial has enrolled more than 6,000 patients at 1,100 sites. A similar approach guided the launch of the Pediatric MATCH Trial, which has expanded to 200 U.S. sites and has enrolled patients in eight therapeutic arms so far.

Greater emphasis also must be placed on recruiting patients to clinical trials from the community setting, Sharpless said.

“Lastly, we have to admit that trials done the old way are inefficient,” he said. “Rather than testing one specific variable in a trial by aggregating data at greater scale, we can learn from every patient. This will require thinking about trials differently, seeing drug development through the lens of a health service researcher, and using the tools of big data and data aggregation.”

Sharpless acknowledged the four priority areas he outlined are highly related, but he emphasized that “other areas not explicitly included” in the vision he outlined will not be ignored.

“NCI is responsible for the entire national cancer program, for research and progress that spans the entire research continuum,” Sharpless said. “We will remain committed to that mission. ...

“We have already made tremendous progress since [the] bad old days of limited options and a poor understanding of the biology of cancer,” he added. “I believe, by applying focus in these areas now, we can further accelerate the pace of that progress.” – by Mark Leiser

 

Reference:

Sharpless NE. NCI and the cancer community: Focusing on patients through innovative research. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.

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