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Monday, April 22, 2019

Major US cancer center ousts ‘Asian’ researchers as NIH flags their foreign ties

The MD Anderson Cancer Center here has ousted three senior researchers after the U.S. National Institutes of Health (NIH) in Bethesda, Maryland, informed it that the scientists had committed potentially “serious” violations of agency rules involving confidentiality of peer review and the disclosure of foreign ties. The researchers are among five MD Anderson scientists that NIH cited in letters to the cancer center, which is part of the University of Texas (UT) system. MD Anderson officials say they invoked termination proceedings against three of the researchers, are still investigating allegations against one, and determined termination was not warranted for the fifth scientist.
The new developments are linked to a sweeping effort launched last year by NIH to address growing U.S. government fears that foreign nations, particularly China, are taking unfair advantage of federally funded research. NIH says its inquiries about the foreign ties of specific NIH-funded researchers have prompted at least 55 institutions to launch investigations. The cases at MD Anderson, which received $148 million in NIH funding in 2018, are the first publicly known instances where NIH’s inquiries appear to have led an institution to invoke termination proceedings against researchers judged to have violated the rules.
Cancer center officials have not named any of the five researchers. MD Anderson President Peter Pisters says all are “Asian”; Science has confirmed that three are ethnically Chinese. Several faced NIH inquiries about their ties to China, according to internal cancer center documents and NIH emails provided by MD Anderson to the Houston Chronicle and reviewed by Science. Those documents also show that MD Anderson has been working with the Federal Bureau of Investigation (FBI) for several years on undisclosed national security investigations, which included searches of faculty email accounts and in one instance, video surveillance. Those investigations could be linked to the recent departures and to the NIH letters; MD Anderson had put at least one faculty member named by NIH on leave in December 2017, months before NIH sent its letter and 1 week after FBI gained access to several MD Anderson network accounts.
MD Anderson’s actions, as well as the larger NIH and FBI efforts, have added to concerns in the Chinese American science community that U.S. officials are targeting researchers for special scrutiny based on their ethnicity. “Scientific research depends on the free flow of ideas,” says Frank Wu, president of the Committee of 100, a group of influential Chinese Americans that is based in New York City. “Our national interest is best advanced by welcoming people, not by racial stereotyping based on where a person comes from.”
Here in Houston, the Chinese American community is also concerned that FBI has not explained why it has been interviewing ethnically Chinese faculty at MD Anderson over the past 17 months. No scientist has been charged with a federal crime. One MD Anderson researcher was charged under state law with a crime unconnected to grant reporting or foreign ties; the charges were ultimately dropped. “We continue to witness several of our distinguished Chinese researchers or scientists accused of infractions without formal charges being levied,” says Rogene Gee Calvert, who co-chaired a panel here on economic espionage.
NIH officials have said they are not engaging in racial profiling. And MD Anderson officials maintain they had little choice but to act after they received letters from NIH detailing allegations and concerns about the five researchers. “As stewards of taxpayer dollars invested in biomedical research, we have an obligation to follow up” when asked to investigate grant recipients, Pisters said in an interview.
Science and the Houston Chronicle have identified at least three other institutions that have received letters from NIH. The letters focus on eight faculty members. Four are at the Baylor College of Medicine, and one is at the UT Health Science Center, all located here. Three work at a major research university that confirmed it received letters from NIH but asked for anonymity. Officials at that university and at Baylor concluded that most of the seven NIH-flagged researchers at their institutions had failed to follow NIH policies, but the violations were not serious enough to merit disciplinary action. The officials said all seven of those researchers were “ethnic Chinese.” There was no public announcement in any of those cases, and it is not clear how other universities have responded to the NIH letters, the most recent of which were sent out last month. The reports “confirm” one or more “serious violations” of NIH or university policies by three researchers. In an additional case, Weber concluded that the researcher did violate some NIH and university policies, but that there were “several ameliorating factors” that argued for a lenient response.
In response to a series of questions from Science, an NIH spokesperson said NIH “does not discuss pending reviews [of the cases highlighted in the letters].” But, the spokesperson added, “NIH commends MD Anderson for their actions [and] encourages other NIH grantee institutions to learn from the MD Anderson experience.”

Specific allegations

The five letters that MD Anderson received from NIH about specific researchers began to arrive late in August 2018. A few days earlier, NIH Director Francis Collins had sent a letter to more than 10,000 institutions warning them of “systematic” efforts by foreign nations to steal intellectual property. In that letter, Collins reminded institutions of NIH rules that bar peer reviewers from sharing confidential grant proposals and require researchers to report ties to foreign institutions, funders, and companies.
Four of the five NIH letters to MD Anderson contain very specific allegations of what NIH terms “serious” rule violations. One letter, for instance, asserts that a researcher had violated peer-review confidentiality by emailing to a scientist in China an NIH grant application marked as containing “proprietary/privileged information.” A different letter alleges that a researcher had shared “detailed information on as many as 8 NIH applications” with a daughter. NIH asserts several researchers had “active and well-supported research programs in China,” or financial ties to foreign firms, that they did not disclose. Three of the letters specifically mention a researcher’s potential involvement in China’s Thousand Talents Program, an effort started in 2008 to establish ties with ethnically Chinese scientists working outside of China by offering funding, salary, and other research support. The letters do not say how NIH learned of the violations it identified, but Collins told reporters after a Senate hearing last week that FBI has “been a major part of providing us with information that they’ve uncovered.” Each letter asked MD Anderson officials to report back within 30 days.
MD Anderson’s compliance and ethics officer, Max Weber, responded with lengthy reports to Pisters, which were provided to the Houston Chronicle in redacted form and reviewed by Science. The reports “confirm” one or more “serious violations” of NIH or university policies by three researchers. In an additional case, Weber concluded that the researcher did violate some NIH and university policies, but that there were “several ameliorating factors” that argued for a lenient response.
Based on those reports, MD Anderson officials say they moved to terminate three of the researchers. Two of those faculty resigned before the termination process was complete; the third person is just beginning due process requirements. A fourth case is still under investigation.

Long-standing FBI interest

Although MD Anderson officials say NIH’s recent letters prompted its actions, the internal documents make it clear that federal law enforcement agents have been examining and interviewing researchers at the prestigious institution since at least 2017. On 11 December 2017, FBI received the cancer center’s permission to obtain information from employee email accounts—as many as 23 accounts, according to sources familiar with the matter—which MD Anderson officials provided on hard drives. During interviews with MD Anderson faculty, FBI agents were interested in obtaining lists of researchers who had accepted grants under the Thousand Talents program, according to one MD Anderson researcher who was interviewed. Supervisory special agent Don Lichay, of FBI’s field office here, would not comment on specific investigations, adding, “We’re just going to go where the evidence is.” A 2015 FBI Counterintelligence Division handout argued that recruiting scientists through programs such as Thousand Talents allows China to “benefit from years of scientific research conducted in the United States” and “severely impacts the U.S. economy.”
This week’s revelations are now fueling complaints among some researchers that MD Anderson is targeting its Chinese and Chinese American scientists for special scrutiny—and removal. Some of the center’s critics count 10 senior MD Anderson researchers or administrators of Chinese descent who have retired, resigned, or been placed on administrative leave in the past 17 months. Some of these researchers reportedly left of their own accord, but their supporters say that a toxic climate and the perception of racial profiling hastened their departure.
“From the Asian-American community perspective, the investigations, in general, came out of the blue and involved only Chinese-American scientists,” says Aryani Ong, an activist in Rockville, Maryland, who has organized several dialogues between community leaders and U.S. intelligence officials on racial profiling. “The fear and confusion may have been mitigated if the institution had first engaged with employees and ensured compliance.”
Calvert says if researchers “are breaking the law and committing a crime, then charge them and let them be tried in a court of law. But what MD Anderson and some other institutions seem to do is accuse and see if they can wait them out.”
Ong is concerned that, as efforts by federal research agencies to address foreign influence take hold, there could be a “brain drain” as scientists “leave under a cloud of suspicion.”
Mien-Chie Hung, a Taiwanese-born researcher who recently left MD Anderson, echoes that view. In  February, Hung retired from his position as the cancer center’s vice president for basic research to take a job as president of China Medical University in Taichung, Taiwan. (His move wasn’t connected to any investigation, he says.) In March, he co-authored a letter to Science raising concerns about possible racial profiling at institutions across the country, expressing hope that “increased security measures will not be used to tarnish law-abiding scientists.”
Pisters says he understands those concerns but rejects the notion that MD Anderson is targeting ethnically Chinese researchers. “In situations where individuals, small in number, have undergone investigations like this, I can understand why groups might feel they’re being singled out,” he says. “That’s not the intent of our organization.”
Some researchers here worry the campaign to root out foreign influence at MD Anderson will be counterproductive and prompt some researchers to leave the United States. “These are the top talents that foreign countries have been trying to recruit unsuccessfully,” says Steven Pei, an engineering professor elsewhere in Houston and a former chairman of the board of United Chinese Americans, a national advocacy organization. (He is not among the 10 people who have departed MD Anderson since 2017.) Institutions like the cancer center, he says, are “helping foreign countries to accomplish what they could not do by themselves.”
This story was produced in collaboration with the Houston Chronicle, with reporting by the Chronicle’s Todd Ackerman, as well as Science’s Jeffrey Mervis and Jocelyn Kaiser.
Click here to read the Houston Chronicle‘s story.

Medidata rises on reported interest by Dassault Systemes

https://thefly.com/landingPageNews.php?id=2895206

FDA clears first device treatment for childhood ADHD

The FDA has cleared the first medical device for treating attention deficit hyperactivity disorder (ADHD): an at-home nerve stimulation system designed for children ages 7 to 12.
The prescription-only treatment—NeuroSigma’s Monarch external trigeminal nerve stimulation system—is designed for children who are currently not taking any medications. About the size of a cellphone, the device delivers a mild electrical pulse to a wired patch placed on the patient’s forehead while sleeping.
By stimulating the branches of the trigeminal cranial nerve, it is believed the system triggers therapeutic signals sent to the parts of the brain involved in ADHD, although the exact mechanism is not known. Neuroimaging studies have shown that eTNS increases brain activity in regions related to attention, emotion and behavior, according to the FDA.
“This new device offers a safe, non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind,” said Carlos Peña, director of the Division of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health, which granted the device a de novo clearance.
In a placebo-controlled clinical trial of 62 children, the Monarch system demonstrated significant improvements in an ADHD symptom scale after four weeks. According to the FDA, it may take at least one month for the treatment to deliver a noticeable effect; after that time, caregivers should consult their providers to reassess the treatment.
While no serious adverse events were observed, the most common side effects were drowsiness, an increase in appetite, trouble sleeping, teeth clenching, headache and fatigue. The device should not be used in patients with implanted pacemakers or neurostimulators, nor wearable insulin pumps.
The Los Angeles-based NeuroSigma previously received a CE mark for its device in late 2015 for use in adults and children over age 7, representing the first nondrug ADHD treatment in the EU. The Monarch system has also received a CE mark in major depressive disorder in patients older than 9.

TytoCare to stock Best Buy on telehealth device for remote doctor exams

Israel-based TytoCare is pairing up with big-box electronics retailer Best Buy to put its remote medical exam hardware directly into the hands of consumers.
Available nationwide through Best Buy’s website for $299.99, the handheld device will also be offered in stores, initially at planned locations in Minnesota, California, North Dakota, South Dakota and Ohio.
The TytoHome telehealth device comes with attachments to examine body temperature as well as the heart, lungs, ears, throat, abdomen and skin to allow for remote diagnoses of ear infections, sore throats, fevers, colds and the flu, as well as allergies, stomachaches, rashes and more.
The company set out to create a medical kit that could “really capture all of those diagnostic data and share it with a clinician as part of a primary care examination,” which it saw as a “missing link” in telehealth, TytoCare CEO Dedi Gilad said in an interview in Israel, as the country prepares to showcase its biopharma industry at next month’s MIXiii BIOMED Conference in Tel Aviv.
Meanwhile, Best Buy said in a statement that the exclusive partnership is another example of the store’s “growing commitment to the health space.” Last year, the retailer acquired GreatCall, which provides connected health and personal emergency response services to the elderly.

TytoCare is also linking up with regional healthcare systems including Sanford Health, a large, not-for-profit system that will provide 24-hour, physician-guided remote exams to home users in Minnesota, Iowa and North and South Dakota. TytoCare also works with telehealth provider LiveHealth Online, powered by American Well, to offer care in other locations.
Through LiveHealth Online, select employers can offer the service to their employees and provide them with coupons to purchase TytoHome at Best Buy, the companies said.
In January, TytoCare raised an additional $9 million in funding to bring its 2018 series C total up to $33.5 million.
The funding round was led by Ping An Global Voyager Fund—with new money from Sanford Health, Itochu and Shenzhen Capital Group and its affiliates—to help fuel strategic partnerships to expand its reach into remote and rural communities in the U.S., Europe, Japan and China.
In China, “it’s not for the mass population right now—Tyto is a bit expensive for that market today,” Gilad said. But the company is working on a cheaper version with a lower-cost electronic platform that “will allow us bigger expansion in China, often at the home level.”

Teva announces U.S. launch of generic version of VESIcare

Teva Pharmaceutical Industries announced the launch of a generic version of VESIcare Tablets, 5 mg and 10 mg, in the U.S. Solifenacin Succinate Tablets are indicated for the treatment of overactive bladder.

CAR-T Drugmaker Poseida Snags $142 Million in Financing Led by Novartis

In January, San Diego-based Poseida Therapeutics eyed a potential $115 million initial public offering to support the development of its CAR-T medicines to treat various blood and solid tumors. The company seems to have scrapped that and instead raised $142 million, with significant support from Novartis.
This morning, the CAR-T drugmaker said Swiss pharma giant Novartis supported the company’s Series C financing round with a $75 million equity investment. For Novartis, which was also the first company in the U.S. to be approved for a CAR-T treatment, the investment in Poseida comes several months after Novartis Chief Executive Officer Vas Narasimhan announced plans at the J.P. Morgan Conference to be on top of the next wave of innovations in gene and cell therapies. Other participants in the round included Aisling Capital Management, Pentwater Capital Management, Perceptive Advisors as well as additional undisclosed institutional investors.
Eric Ostertag, Poseida’s chief executive officer, touted the support from Novartis, a company with a keen focus on cell and gene therapies. Ostertag said the financial support will allow the company to accelerate its pursuit to “create gene therapy product candidates that could result in single-treatment cures for numerous oncologic indications and orphan genetic diseases, with an initial focus on chimeric antigen receptor T cell (CAR-T) therapies.”
Poseida’s lead product candidate is P-BCMA-101, which is being developed for relapsed/refractory multiple myeloma. Poseida is currently enrolling patients in a Phase II registrational trial with outpatient treatment – meaning the patients won’t have to be admitted to the hospital for post-treatment monitoring. Initial dosing is expected to begin in the first half of 2019, the company said.
At the 2018 American Society of Hematology meeting in December, Poseida revealed data that showed all 23 patients in each of the five cohorts had responded to P-BCMA-101 and showed improved markers of disease. Overall, of the 19 patients evaluable by International Myeloma Working Group criteria, 15 showed meaningful responses, including 13 who reached stringent complete response, complete response, VGPR or partial response, the company said. Of those, five showed stringent complete responses, the company said. P-BCMA-101 was well-tolerated. The company also said that cytokine release syndrome was very low, with just five cases that were “mild and transient” across all doses.
Other CAR-T products in preclinical development include autologous and allogenic products aimed at castrate resistant prostate cancer, relapsed/refractory multiple myeloma and numerous solid tumors, including ovarian, breast, lung, colorectal, pancreatic and renal cancers. Poseida said it is planning on filing Investigational New Drug Applications with the U.S. Food and Drug Administration for these candidates in 2019 and 2020.
Poseida plans to broadly advance its current CAR-T programs and emerging pipeline programs, including gene therapies for orphan genetic diseases.
The company’s CAR-T product candidates are manufactured with Poseida’s non-viral piggyBac DNA Modification System, resulting in a high percentage of stem cell memory T cells (TSCM). Tscm cells are the only T cell that is self-renewing and long-lived, potentially resulting in product candidates that are more efficacious, less toxic and more durable.

Humana: ‘Unhealthy Days’ For Seniors Drop As Social Determinants Screened

A project by Humana to improve the health of seniors through better management of patient populations in seven U.S. cities continues to show improvement, the company said in a new report out Monday.
The health insurer’s “Bold Goal” initiative uses measures established by the Centers for Disease Control and Prevention to track an individual’s physical and mental “unhealthy days” over a 30-day period. The social determinants of health for these patients are closely watched with patients screened for “food insecurity” and “loneliness.”
“The social barriers and health challenges that our Medicare Advantage members and others face are deeply personal,” Humana chief medical officer Dr. William Shrank said in a statement accompanying the report. “This requires us to become their trusted advocate that can partner with them to understand, navigate and address these barriers and challenges. With ‘healthy days’ as our barometer, we are able to track and trend population health, measure outcomes and triage members in unique ways to the resources they need.”
The original seven Bold Goal communities are Baton Rouge, Knoxville, Louisville, New Orleans, San Antonio, Tampa Bay and Broward County, Florida, and most have improved since the effort began four years ago.
“Medicare Advantage members living in the company’s original seven Bold Goal communities have seen a 2.7% reduction in their unhealthy days since 2015,” Humana said in its report. “In San Antonio, Texas, members saw a 9.8 percent reduction in Unhealthy Days, which means they are halfway toward their Bold Goal.”
Over time, Humana has expanded the number of Medicare Advantage enrollees screened as evidence has shown the overall effort has worked. “With the help of internal business partners, physician practices and community-based organizations, we screened over 500,000 people for food insecurity and loneliness and connected those who screened positive to community resources,” Humana’s report said. “We set a new goal of screening 1 million people by the end of 2019.”
Humana’s population health initiative comes as health plans move away from fee-for-service medicine that pays doctors and hospitals based on the volume of care delivered to value-based models that measure the success of health outcomes. Blue Cross and Blue Shield plans, Aetna, Cigna and UnitedHealth Group are also working on similar value-based models and programs in communities as well as shifting most payments from fee-for-service to alternative reimbursements.
Meanwhile, more seniors are signing up for Medicare Advantage plans, which contract with the federal government to provide extra benefits and services to seniors, such as disease management and nurse help hotlines, with some also offering vision, dental care and wellness programs. The Centers for Medicare & Medicaid Services is changing regulations to allow Medicare Advantage plans to provide broader coverage in the future, which is also expected to boost enrollment already at more than 22 million this year and headed to nearly 40 million, or half of the U.S. Medicare population by 2025, some have projected.
“This year’s report reflects our track record of success in managing chronic conditions over time,” Humana CEO Bruce Broussard said. “Given current demographic trends, we expect to see continued demand for a support structure that addresses social needs, along with clinical ones.”