Sunday, February 01, 2015

Ethics and Stem Cell Research Symposium Feb. 12: Gordie Howe to Right to Try

The public and other interested parties are invited to a UC Davis bioethics symposium Feb. 12 that is likely to deal with some high profile issues involving stem cell research.

Davis researcher Paul Knoepfler is helping to organize the event which he said will include stem cell tourism (think former hockey great Gordie Howe), Right to Try laws and much more. The panelists include Timothy Caulfield of the University of Alberta and Leigh Turner of the University of Minnesota.

A blogger by the name of HappyAnise wrote on the StemcellPromise blog,
“What it makes this so exciting is that they’re apparently going to be talking about some REAL, GENUINE ethical issues. To wit… what on earth are we going to do about all of those stem cell clinics popping up in various and assorted countries? You know, the ones with the weird, dubious, expensive treatments that the FDA would never approve in a gazillion years? And while we’re on the subject, when is the FDA going to do anything about regulating, say, $10,000 stem cell creams? And what about those “Right to Try” laws? They passed in four states in November, but what is the federal government going to do, if anything? What should they do?”
You can register with at 916-734-6181 or julie.bechtel@ucdmc.ucdavis.edu.



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Saturday, January 31, 2015

California's New, Fast-Track Stem Cell Program Draws Applications But Details Missing

California’s new and ambitious effort to speed stem cell therapies into widespread use drew “multiple” applications as it closed out its first round on Friday.

January is the first month of what the agency calls a radical move in its grant-making. Its initial foray is a $50 million clinical stage round that will be accepting applications for funding at the end of each month until the middle of the year.

The promise for those filing Friday is to put money in their hands in roughly four to five months. That compares to an average of 22 months under the agency’s previous grant rounds.

Randy Mills, the president of the agency, devised the fast-track effort and dubbed it CIRM 2.0. He told agency directors on Thursday that “multiple applications” had been received. (See here and here for more on CIRM 2.0.)

The California Stem Cell Report on Thursday and Friday asked for the specific number that Mills referred to. The agency, formally known as the California Institute for Regenerative Medicine(CIRM), however, did not provide a figure. 

The requests from the California Stem Cell Report also sought the following, all of which is public information: the total number of applications, the number from academic institutions, number from nonprofits, number from businesses, figures on the amount being sought on each application and the general nature of the research proposed.

Applications were due by 5 p.m. PST Friday. Presumably the agency will have the complete information assembled by early Monday and will provide it then. 
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The Stem Cellar: California Stem Cell Agency on Gordie Howe and Human Tissue Donations

The Stem Cellar is the blog of the California stem cell agency, and it is consistently worthy of attention.

For the most part it deals with scientific issues, only occasionally touching on other matters. Of course, it does serve as a vehicle for selling the agency’s programs and informing readers about their benefits.

On Friday, the Stem Cellar dealt once again with the Gordie Howe stem cell treatment situation, which received a fair amount of attention over the holidays in December.

The case involved a San Diego firm and treatment of the famed hockey star in Tijuana. Most of the coverage in the mainstream media has largely accepted the claims that the treatment has been wildly successful.  

Anne Holden, Web content and social media manager, wrote on Friday, 
“Finally some healthy skepticism has arrived. Hockey legend Gordie Howe’s recovery from a pair of strokes just before the holidays was treated by the general media as a true Christmas miracle. The scientific press tried to layer the coverage with some questions of what we don’t know about his case but not the mainstream media. The one exception I saw was Brad Fikes in the San Diego Union Tribune who had to rely on a couple of scientists who were openly speaking out at the time. We wrote about their concerns then as well.
"Now two major outlets have raised questions in long pieces back-to-back yesterday and this morning. The Star in hockey-crazed Canada wrote the first piece and New York Magazine wrote today’s. Both raise serious questions about whether stem cells could have been the cause of Howe’s recovery and are valuable additions to the coverage."
Holden, who was trained as a genetic anthropolgist, also wrote on another subject.
“A University of Michigan study suggests most folks don’t care how you use body tissue they donate for research if you ask them about research generically. But their attitudes change when you ask about specific research, with positive responses increasing for only one type of research: stem cell research.
“On the generic question, 69 percent said go for it, but when you mentioned the possibility of abortion research more than half said no and if told the cells might lead to commercial products 45 percent said nix. The team published their work in the Journal of the American Medical Association and HealthCanal picked up the university’s press release that quoted the lead researcher, Tom Tomlinson, on why paying attention to donor preference is so critical:
“'Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.'
“CIRM has begun building a bank of iPS-type stem cells made from tissue donated by people with one of 11 diseases. We went through a very detailed process to develop uniform informed consent forms to make sure the donors for our cell bank knew exactly how their cells could be used. Read more about the consent process here.” 
We should also note that The Stem Cellar is several notches above what the agency used to produce several years ago for a blog. It is informative, explanatory and accessible and improving even prior to Holden's hiring.
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Friday, January 30, 2015

Winners Revealed for $30 Million in California Stem Cell Awards

The California stem cell agency today revealed the identities of the winners of $30 million in awards aimed at removing bottlenecks in stem cell research.

The 20 names were added to the news release posted yesterday afternoon on the agency’s Web site. All the recipients work at institutions that have representatives on the agency’s governing board. Those representatives are not allowed to vote on the applications from their institutions, but they set the rules for and the scope of the research that is being funded.

Today’s posting of the names is a departure from past practices. Previously the agency would release the names on the day when the agency board approved the grants. Yesterday, the agency moved quickly to publish the main body of the news release on the action, minus the names.

The list contains the number of each application, but without a link to the summary of reviewer comments on the proposals.  The reviewer comments cannot be found by searching on the application number on the CIRM Web site.

Instead, a search on application numbers on the CIRM Web site will turn up only an abstract and statement of public benefit prepared by the researcher.

The review summary, which contains more details and something of a critique, can only be found in a 162-page, omnibus document given to board members and posted on the meeting agenda. It encompasses all the application review summaries along with scores and staff comments.  That document, which is much more valuable to the public and the scientific community than the abstract and benefit statement, can be found here.  

(Editor's note: Following publication of this item, Kevin McCormack, senior director of communications for CIRM, sent the following concerning the statement that representatives of institutions receiving awards are not allowed to vote on applications from their institutions.

("That's not quite right. In fact, it's not right at all. Representatives of institutions are not allowed to vote on any applications at all, not just those that involve their own institutions. They can't vote on any funding or award.")
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Thursday, January 29, 2015

Evaluation of California's Stem Cell CEO Caps Today's Board Meeting

Directors of the California stem cell agency have gone into executive session to discuss evaluation of its new president, Randy Mills, who has been on the job since last May. No major additional action is expected from the board. The California Stem Cell Report does not expect to file additional items later today. But check the articles below for earlier board action today on $30 million in grants, sweeping proposed rules for stem cell grants and termination of the $131 million CIRM scholars program. Sphere: Related Content

From Fraud Checks to Unspent Funds: California's Proposed Rules for Stem Cell Researchers

The California stem cell agency today put off adoption of  new rules for the way it will hand out its last $1 billion, speeding the money to researchers and attempting to improve the quality of research proposals.

The agency's staff deferred action on the proposal in order to spend more time refining it prior to action in March. The interim grant administration rules are designed to implement the CIRM 2.0 plan laid out by agency president Randy Mills, who has been on the job since last May. 

The rules will apply to the initial phase of CIRM 2.0, which closes the first of its new, rolling application rounds tomorrow, and is subject to adjustment. CIRM (the California Institute for Regenerative Medicine) expects to extend the new rules in one form or another to all upcoming award rounds.

The agency calls the fast-track effort a radical change from previous years. It is certain to have a major impact on many scientists.

The agency is funded by money that the state borrows (bonds). It has handed out roughly $2 billion and figures its remaining $1 billion will last until about 2020 when it will need additional financing.

The new regulations talk about such things as “real-time course corrections,” background fraud checks, early and stringent budget review, restrictions on appeals by rejected applicants and elimination of paper work.

Here are some excerpts from an agency memo identified as coming from the “legal team.”  It unfortunately does not contain a marked-up version showing language that has been deleted from the previous grant administration policy along with the new language.

Money

“Prior to CIRM 2.0, payments to grantees were made primarily based on the calendar – disbursements keyed off the start date of the project and were periodically made based on some given period of time following that date. Under the proposed GAP(grant administration policy), however, for clinical stage projects, CIRM will shift to a milestone-based payment schedule. Thus, this section of the GAP describes the importance of the milestones and how payments on the grant will only be made upon successful completion of the milestones.

“Additionally, in many circumstances the grantee will be allowed to keep unspent CIRM funds upon successful completion of the project, to be spent on any other project of the grantee’s that is consistent with advancing CIRM’s mission. This new process will incentivize grantees to advance the project in the most efficient and shortest time possible, fulfilling CIRM’s goal to accelerate such projects.”

Background checks

“The eligibility section has been drafted to reflect that applicants will undergo a background check to ensure no prior or pending records of fraud or misuse of funds.” 

Budgets

“This new review will examine the proposed budget to identify where proposed costs diverge from established market rates and where opportunities for budget tightening may be found. To incentivize efficient budgeting, where CIRM determines that a budget differs significantly from market rates, conforming adjustments will have to be made before the application will be brought forward for review by the GWG (the grant review group).” 

Fast-track

“Rather than require submission of extensive documentation regarding compliance with myriad protocols and processes – some CIRM-imposed and others external – the proposed process will rely on certification of compliance by the applicant, with the ability for CIRM to request supporting documentation if cause to do so arises.” 

Elimination of paper work

“Because most prior approval requests were routinely granted, and therefore added little value to the process, prior approval requests for rebudgeting and carryforward have been eliminated. We have also eliminated prior approval requests for no-cost extensions because our new CIRM awards will have project end dates that will be extended automatically as needed to complete the final Operational Milestone. CIRM intends to increase the latitude for grantees to pursue their research, while maintaining visibility into and approval of any changes to key components of clinical trials, manufacturing processes, or any other activities that meaningfully impact milestones or suspension events.” 

Clinical advisory panels (CAP)  for each award

“CAPs will provide real-time course correction and will focus more on acceleration opportunities than pure evaluation. CAPs will be tailored for the needs of each project and will consist of CIRM and external members, more nimbly sized than prior CDAP panels. CAPs will meet on a quarterly basis (instead of annually with CDAP) and examine all relevant information regarding project progression, possible roadblocks, and avenues for progression.” 

Appeals from rejected applicants

“Finally, in light of the rolling nature of the programs which will allow unsuccessful applicants in many instances to reapply with improvements to their applications, CIRM will limit the grounds for appeal of Scientific Review to those based on demonstrable conflicts of interest (as defined in the conflict of interest policy applicable to GWG members).”
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Stem Cell Research Training Program Terminated by California

The California stem cell agency today scuttled its first grant program, a $131 million effort to train stem cell scholars at time when researchers were backing away from the field.

The 29-member governing board voted, 14-5, to end the program that began in 2005 as an effort to demonstrate that the research effort was still kicking while legal challenges threatened its existence. The vote came on a recommendation by the agency's staff.

Arlene Chiu, who is now with the City of Hope, was the chief scientific officer for the agency when the program was launched. She told agency directors said it was time to rethink the program, which was aimed at bringing more scientists into the field. She said,
"Its success has removed its necessity."
Chiu said stem cell research is currently attracting a growing wave of interest among younger scientists. The agency said some training would be included in future research programs.

(Editor's note: The chart on the training program was added to this item after it was initially posted.) Sphere: Related Content

CIRM Press Release on $30 Million in Awards

The California stem cell agency has posted a news release on approval of $30 million for 20 projects to clear out roadblocks hampering the development of stem cell cures. A list of recipients will be forthcoming later, the agency said. Sphere: Related Content

California Okays $30 Million in Awards to Help Remove Stem Cell Roadblocks

Directors of the California stem cell agency today approved $30 million to help eliminate bottlenecks in turning stem cell research into cures.

The action gave the go-ahead to awards that were backed by either its blue-ribbon reviewers from outside of California or the agency’s own staff, plus three additional proposals moved forward by the board.  The agency has already spent $52 million to develop stem cell research tools. Today's round was originally budgeted for $35 million.

After a brief discussion, the 29-member board approved, 9-2, an award to UC Davis researchers who had appealed rejection of a $1.8 million proposal by the staff of the California Institute for Regenerative Medicine (CIRM), as the $3 billion agency is formally known.

The agency did not immediately release the names of the winners. It keeps the names of all applicants secret until after the board ratifies the actions of its reviewers, who make the de facto award decisions for the agency behind closed doors.  The agency is expected to issue a press release on the awards later today. (Here is the link to the press release. It does not include a list of recipients.)

The board did not vote on two applications on which appeals were filed involving material misstatement of facts. Those were deferred  until the March board meeting. The final four numbers of those applications are 7836 and 7678.

Here is a link to the document on this "tools and technology" round submitted to the board by its staff. Summaries of the reviews can be found with the document along with the scores on the winners.
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Discussion Underway in $35 Million in California Stem Cell Grant Round

Directors of the California stem cell agency have begun discussion of awards in a $35 million round to remove bottlenecks in stem cell research. Here is a CIRM list of board members that have conflicts on specific applications. Those board members are not allowed to discuss those applications or vote on them.
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California Stem Cell Directors Open Meeting Today in California

Directors of the California stem cell agency opened their meeting today in Burlingame, Ca., at 9 a.m. PST with introduction of new board members. Sphere: Related Content

Former Top Exec at Stem Cell Agency Appointed President of Huntington Medical

The former chief scientific officer of the California stem cell agency, Marie Csete, yesterday was named the president of the $53 million Huntington Medical Research Institutes in Pasadena, Ca.

Marie Csete, Huntington photo
Csete left the stem cell agency in 2009, after serving for a little more than a year. Her departure involved tension between her and former agency President Alan Trounson.  She told the journal Nature,
"When it became clear to me that my considered clinical advice was not respected, I concluded that it made no sense for me to stay at CIRM.”
Csete was the last person to hold the position of chief scientific officer at the agency. Trounson left the agency in July last year.

Huntington reported assets of $53 million in late 2013 and funds a wide variety of research. 
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Wednesday, January 28, 2015

California Stem Cell Appeal: $1.8 Million Needed for Removing Bone Replacement Bottleneck

A UC Davis researcher is making a strong pitch to the California stem cell agency to finance a $1.8 million effort to “resolve bottlenecks in engineering replacement bone and cartilage.”

J. Kent Leach, UC Davis photo

J. Kent Leach, an associate professor in the departments of biomedical engineering and orthopedic surgery, said his proposal addresses “a major hurdle in regenerative medicine of the musculoskeletal system (that) impairs the inherent personalized medicine component of stem cell-based methods.”

In a letter to the agency’s board for its meeting tomorrow, Leach said the research team involved is “arguably the most qualified team in the nation to conduct these studies.” 

Other scientists participating are Laura Marcu and Kyriacos Athanasiou.

Kyriacos Athanasiou
UC Davis photo
Reviewers for the $3 billion agency, who make the de facto decisions on awards, scored the application at 72 and did not approve it for funding. The agency’s staff also nixed the proposal, declaring,
“There is another application recommended for funding in Tier 1 that proposes to optimize and apply the same imaging technology platform to a different test system. In addition, the scientific leadership of the two applications is the same.”
Leach said,
“The co-PI (Dr. Marcu) of this proposal is also PI (principal investigator) on RT3-07879, which is focused on assessing stem cell repopulation and remodeling of engineered vascular tissue constructs. 
Laura Marcu, UC Davis photo
"However, the use of this technology for monitoring the maturation of engineered bone and cartilage, tissues composed of dense matrix reflective of the differentiation of contributing stem cell populations, is substantially different from cardiovascular applications. Of course, both applications involve instrumentation based on optical spectroscopy and ultrasound principles, but the implementation and subsequent commercial hurdles for this technology is very different.”
 (For the summary of reviewer and staff comments, see application RT3-07981 in this document.)

Leach noted that another competing application in the round received an identical 72 score and was approved by the agency’s staff.

The grant round was budgeted for as much as $35 million. Reviewers and CIRM staff recommended approval of awards totaling $29.2 million.

Scientists making appeals directly to the board have not been successful in the last 12 months or so. The board has been more reticent about overturning reviewer and staff recommendations since it changed review and appeal procedures in 2013.
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Follow Complete Coverage of Tomorrow's California Stem Cell Meeting

Keep track of all the “thrills and chills” at tomorrow’s meeting of the governing board of the $3 billion California stem cell agency with gavel-to-gavel coverage from the California Stem Cell Report.

This blog will monitor the session via the Internet from our perch in Banderas Bay in Mexico and file stories as warranted. On tap is as much as $35 million in awards. Reviewers and agency staff have approved only $29 million. But three UC Davis researchers are seeking another $1.8 million.  

Also up for action are major changes in the administration of grants – all part of the CIRM 2.0 effort designed to fast-track cash and beef up the quality of applications.

The session, scheduled for eight hours, can also be heard via a listen-only audiocast and Webcast for the slides being used.  Teleconference locations where the public can attend and comment are also available in Sacramento, Irvine and two in La Jolla.  Specific locations and directions for the Internet access are available on the agenda.  

The meeting begins at 9 a.m. PST in Burlingame.
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Tuesday, January 27, 2015

Bump on CIRM 2.0 Speedway: California's Missing Stem Cell Loan Rules

When the applications come in this Friday for the California stem cell agency’s new, $50 million stem cell research round, business applicants will not be seeing a substantial portion of key financial rules for the awards.  

Missing will be the terms of loans that the agency expects to offer to for-profit enterprises. Loans -- rather than grants -- have been the favored method of businesses for receiving awards. The reason is that the agency’s loans have been forgivable if the research does not generate an appropriate amount of cash for the company. Grants, on the other hand, carry requirements for royalty payments. (None have been generated.)

Under the terms of the fast-track, CIRM 2.0 applications, businesses will have the choice of grants or loans. New grant terms are expected to be approved at Thursday’s meeting of the governing board of the $3 billion agency, one day before the deadline for applications for the first round of CIRM 2.0.

Action on new loan rules was originally scheduled for this week but postponed a few days ago after the agenda was posted Jan. 17. The specific reasons are not entirely clear.  The California Stem Cell Report yesterday asked about the delay and for a copy of the latest loan proposal. Kevin McCormack, senior director for communications, replied, 
“We are in the process of revising the (loan policy) and nAeeded additional time to ensure alignment with CIRM 2.0 and the other policy changes so we postponed the meeting.  It will be rescheduled before the March board meeting.
 “And as we are still working on the loan policy it would be premature to share that with you right now, it's still a work in progress.”  
Given that businesses have amounted to a tiny percentage of awards in the past, the delay in the loan rules question may not be significant. But this round is aimed at clinical stage projects, which are more likely to involve businesses and could generate more applications from the private sector.

Some time is available to adopt new rules before CIRM board action on the awards, possibly during an April 23 telephonic meeting. But one of the main points of CIRM 2.0 is to put cash in the hands of recipients significantly faster than in the past. This is especially important for stem cell companies, which are always pretty much cash starved.

Delays in any portion of the aggressive timetable for CIRM 2.0 could mean delays in handing out money.

It is not surprising that some difficulties have arisen in the new award procedures. Randy Mills, CEO of the stem cell agency, last week told an Internet audience of about 200 there would be “some bumps.” He said,
“This is going to be one wild ride.”  
To help smooth it out for both the agency and applicants, it would behoove the agency to post the proposed loan terms in a timely fashion. That means that they should be available to the public when a meeting agenda involving the rules – be it for a subcommittee or full board meeting -- is posted on the CIRM Web site. That is normally 10 calendar days ahead of the session.  The agency, which is costing taxpayers $6 billion including interest, doesn’t need any more mysteries.
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Monday, January 26, 2015

$131 Million and 887 Papers: Demise of California's First Stem Cell Grant Program

The $3 billion California stem cell agency on Thursday is expected to put to rest its oldest grant program – an effort that was begun with bravado in 2005 but minus the cash to back it.

It was a matter -- at the time -- of showing the Golden State’s stem cell flag despite legal challenges that had stalled the progress of the agency.  The grants were the agency’s first and came on a late summer day in Sacramento during a governing board meeting marked by confusion and frustration.

David Baltimore
PasadenaNow photo
Board members complained they did not have enough information to make good judgments on the awards. 

Nobel Prize winner David Baltimore, a board member and president of Caltech, objected to what he considered loose standards in evaluating the applications for millions of dollars.

At one point, a crusty reporter from The Associated Press, Paul Elias, jumped up and demanded to know exactly what was going on.

The headline on the story the next day in the California Stem Cell Report said, 
“CIRM Hands Out $39 Million (sort of)….”
The awards created a training program for stem cell scientists. It was aimed at attracting more researchers into a field that was atrophying because of the Bush administration’s restrictions on stem cell research funding. 

Without adequate financial resources, the California Institute for Regenerative Medicine (CIRM), as the agency is formally known, appealed to the recipient institutions to advance the funds with the expectation they would be reimbursed later.

Zach Hall, who was appointed president of the agency the same day, called the awards “historic.” Robert Klein, the chairman of the CIRM board, said he was thrilled by the program.

One of the major goals of the board action was to show that the agency and that its tiny staff (something less than 20) was still kicking despite the legal dispute that blocked issuance of the bonds that provide funding for the agency. 

In that regard, CIRM was more than successful.  The meeting was well-covered by major newspapers in the state, a far cry from the situation today. The message in the stories was largely favorable. The California Stem Cell Report wrote on Sept.11, 2005,
“Subordinated was the reality that the agency does not yet have the money. Even more deeply subordinated were complaints about the grant process from critics.”
The initial awards ultimately grew into a nine-year, $131 million effort. In a Jan. 20 memo to the CIRM board, the agency’s current president, Randy Mills, said,
“The programs have trained 859 CIRM Scholars. These trainees have worked in 436 different laboratories on a broad range of research projects, with the majority focused on basic research. CIRM Scholars have been authors on 887 scientific publications.”
The average cost for each “scholar” was about $152,000, Mills reported. The California Stem Cell Report calculated an average expense of about $148,000 for each scientific article, although such articles usually have more than one author. Mills said 34 percent of the recipients were graduate students, 48 percent post-doctoral and 18 percent clinical fellows.

Not noted by Mills was the fact that nearly all the awards went to institutions linked to members of the agency’s governing board. Virtually no other institutions existed, however, in California that could provide the training.

In December 2013, the board asked the agency staff to prepare a new version of the training program, a task that was not completed before the board hired Mills last spring.

In his memo last week, Mills said that “the CIRM team determined that a new training grant program is no longer an optimal method of supporting the education and training of stem cell scientists.” He continued,
“CIRM believes that supporting the training of new stem cell scientists is best accomplished by bolstering funding for our research grants programs, particularly the earlier discovery and translational phases where each program can be individually evaluated for its merit and contribution to CIRM’s mission.”
Mills said he will present concept plans for new discovery and translation rounds, including training within them, during the next six months. And he asked the board to approve his recommendation to drop the plans continue the old, once-hailed training program.
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