Stem Cell Agency Plan Falls Far Short of Solving IOM Concerns

The governing board of the $3 billion California stem cell agency last week fell far short of complying with the recommendations of a blue-ribbon Institute of Medicine (IOM) study that the agency itself commissioned to improve its performance.

Many of the proposals by the IOM dealt with conflicts of interest at the eight-year-old agency, which board members reluctantly recognized on Wednesday as a perception problem. Under the plan approved last week, 13 of the 29 members of the board would not be allowed to vote on any awards. They are members tied to institutions that benefit from funding. Three other board members linked to those beneficiary institutions, however, would still be allowed to vote on grants other than those to their institutions. .

The board did nothing to deal with the structural issues involving conflicts of interest that are built into the board as the result of Prop. 71, the ballot measure that created the research effort in 2004. The 29-member board was constituted in such a way as to give nearly all institutions that could benefit a seat at the table where the money is handed out. It is as if the state's Public Utility Commission, which sets utility rates, were dominated by executives of the utility companies.

Under longstanding rules, individual members of the stem cell board are barred from voting on grants to their institutions. However, the board still determines the game and the rules. The board approves the specific areas of research for funding, approves plans for individual RFAS, sets the rules for the grants and loans and enforces compliance through CIRM staff.

The board last week limited itself to changes that it could enact on its own. Many of the IOM recommendations, including a new majority of independent members, would require legislative action, which opens the agency to a wider range of changes than even the IOM recommended. That is not a prospect the agency relishes. Nonetheless, how well the board complies with the IOM recommendations is likely to be critical to its plans to raise funds to continue its operations beyond 2017, when the taxpayer cash runs out for new grants.

Here is a look at the key IOM recommendations and the response so far from the stem cell agency(see here and here). More details may emerge between now the next CIRM board meeting in the San Francisco Bay Area March 19, when the board is schedule to finalize its IOM plan. 

IOM Recommendation

“Change the Composition and Structure of the Board and Working Groups.

“CIRM should put systems in place to restructure the board to have a majority of independent members, without increasing the size of the board. It should include representatives of the diverse constituencies with interests in stem cell research, but no institution or organization should be guaranteed a seat on the board. Consideration should be given to adding members from the business community....The chair and other ICOC members should be prohibited from serving on the working groups. During the reconstitution of the working groups, the current level of representation of disease advocates should be maintained, such board members being replaced with other disease advocates who are not board members.”

CIRM Response

The Thomas plan basically is a total rejection of this recommendation. The CIRM board does not support creation of a new majority of independent members, which would mean some current members would lose their seats if the board were not increased beyond 29 members. No members will be added from industry. Board members will continue to serve on the grant review panel and other groups, contrary to IOM recommendations. In the case of grant reviews, however, they would no longer vote in the closed door sessions. The board has no plans to add patient advocates who are not board members to working groups, including the grant review panel. The University of California will continue to have five guaranteed seats on the board. No independent members currently sit on the board.

IOM Recommendation

“Revise Conflict of Interest Definitions and Policies.

“CIRM should revise its definitions of conflict of interest to recognize conflicts arising from nonfinancial interests, such as the potential for conflict arising from an individual’s interest in a specific disease, and should reassess its policies for managing conflict of interest in light of this broader definition.”

CIRM Response

CIRM has no plans to move to prevent nonfinancial conflicts of interest. Several board members expressed strong opposition to such an effort. Sixteen persons who sit on the board have ties to institutions that receive CIRM funds. Currently individual board members cannot vote on applications from their institutions. To avoid the appearance of conflicts of interest, the Thomas plan would have the 13 members directly appointed from beneficiary institutions voluntarily abstain from voting on any grant applications. Apparently not affected under the Thomas plan would be three other board members who are appointed as patient advocates. Two of them are employed by beneficiary institutions. The third is chairwoman of the UC Board of Regents. All of the board members would continue to vote on plans for all rounds of grants, including determination of some of the specifics of the ensuing RFAs.

IOM Recommendation

“Restructure the Grant Review and Funding Process.

“CIRM should restructure the grant review and funding process to separate oversight and strategic planning from day-to-day operations. The ICOC (the agency's governing board) should remain responsible for oversight and articulation of an overall strategic plan. However, grant management, funding recommendations, and grant administration should be the responsibility of the CIRM scientific staff, reporting to the president. This restructuring would help mitigate concerns related to conflicts of interest and would also put the review and funding process in the hands of those best equipped to make those decisions.”

CIRM Response

CIRM patient advocate board members who serve on the grant review group would not vote on applications during the grant review sessions. They would be limited to voting at public board meetings. They would lead discussion of non-scientific considerations for approval of applications during the public sessions. Currently that occurs during the closed door review.

IOM Recommendation

Abolish the “extraordinary petition” mechanism for public appeals of negative grant reviews.

CIRM Response

Move all appeals to staff level and behind closed doors. Currently extraordinary petitions are handled in public board meetings, sometimes leading to lengthy, emotional sessions with presentations by patient advocates. The public in general, including grant applicants, continues to have the right under state law to address the board on grant applications or any other matter they wish.

IOM Recommendation

“Separate Operations from Oversight.

“The board should focus on strategic planning, oversee financial performance and legal compliance, assess the performance of the president and the board, and develop a plan for transitioning CIRM to sustainability. The board should oversee senior management but should not be involved in day-to-day

management. The chair and the board should delegate day-to-day management responsibilities to the president. Each of the three working groups should report to management rather than to the ICOC.”

CIRM Response

The Thomas plan does not appear to differ significantly from current operations, which reflect the troubling dual executive arrangement involving the chairman and president that was created by Prop. 71, the ballot measure that created CIRM. The existing arrangement is also a hangover from the days of the agency's first chairman, Robert Klein, and has been an obstacle in previous recruitment efforts for a president of the agency. The Thomas plan does eliminate a dual reporting arrangement for the chief financial officer, a position that has been vacant since last summer. Thomas indicated last fall that the position would not be filled. Both the chairman of the IOM study panel and the California state controller's office both say more needs to be done to separate operations from oversight.

IOM Recommendation

“Enhance Industry Representation in Key Aspects of CIRM Organization.

“Industry representation on the ICOC, the Scientific Advisory Board, the Standards Working Group, and the Grants Working Group should be enhanced to leverage industry’s expertise and resources in product development, manufacturing, and regulatory approval in support of the ultimate goal of bringing therapies to patients.”

CIRM Response

The Thomas plan would increase industry involvement “where appropriate.” However, industry has complained for years about this problem, and some board members as well. But little has been done to deal with the problem. Recently, the agency has taken some steps to engage industry, but the IOM was aware of those when it made its recommendation for closer cooperation.

IOM Recommendation

“Establish a Scientific Advisory Board.

“CIRM should establish a single Scientific Advisory Board comprising individuals with expertise in the scientific, clinical, ethical, industry, and regulatory aspects of stem cell biology and cell-based therapies.” Members of this board would be from out of state and replace existing advisory boards. They would be appointed by and report to president.

CIRM Response

CIRM says the structure and membership of the a new board is under discussion, but generally indicated it would go along this proposal. Not specifically addressed was abolition of other advisory groups.

Develop a “sustainability” platform in consultation with current and future partners, including sources of funding.

IOM Recommendation

Develop a “sustainability” platform in consultation with current and future partners, including sources of funding.

CIRM Response

Chairman Jonathan Thomas said he is working on details of a plan.

IOM Recommendations

“Incorporate Future Enforcement of Intellectual Property Policies in the Sustainability Platform.

“As part of the plan maximizing the continued impact of CIRM’s many achievements..., CIRM should propose regulations that specify who will have the power and authority to assert and enforce in the future rights retained by the state in CIRM-funded intellectual property.”

“Consider Harmonizing Intellectual Property Policies with Policies of Bayh-Dole Act.

“As other sources of funding for stem cell research become available and as the field of regenerative medicine advances from the laboratory to the clinic, the ICOC should reconsider whether its goal of developing cures would be better served by harmonizing CIRM’s IP policies wherever possible with the more familiar policies of the Bayh-Dole Act.”

CIRM Response

The governing board's IP Subcommittee will review the policies and make recommendations.

CIRM's Thomas: Conflicts 'Put to Bed' at Stem Cell Agency

The chairman of the $3 billion California stem cell agency, Jonathan Thomas, today hailed board action last week as putting “to bed once and for all” questions about financial conflicts of interest by members of the agency's governing board.

Writing on the agency's blog, Thomas pointed to board approval of a new policy that would bar 13 of the 29 members of the governing board from voting on any grants whatsoever. The 13 are the members who are “appointed from an institution that is eligible to receive money.” Three other board members have ties to institutions that receive money. Two are employees of the institutions and one is the chair of the University of California board of regents, Sherry Lansing. All three are appointed as patient advocate members of the board. Currently all 16 are barred individually from voting on grants to their institutions, but they can vote for awards to other institutions.

Thomas proposed the plan last week to the governing board, which approved it on a 23-0 vote with one abstention. Thomas advanced the proposal in response to the recommendations of a 17-month study by the Institute of Medicine(IOM). CIRM paid $700,000 for the blue-ribbon report, hoping that it would serve as the basis for continued financing of the agency beyond 2017, when funds for new grants run out.

The IOM's far-reaching recommendations included creation of a majority of independent members on the board, which would mean some current members of the board would lose their seats. No institutions would be guaranteed seats on the board. Currently five members are appointed from the University of California. The Thomas plan does not deal with those recommendations.

The IOM said “far too many” members of the board have ties to institutions that receive funds from CIRM. Compilations by the California Stem Cell Report show that about 90 percent of the $1.7 billion that the board has awarded has gone to institutions linked to directors.

Thomas said that the board last week “endorsed a framework of proposals that would dramatically change the way the board works, and directly addresses the concerns and recommendations of the IOM, in particular their feeling that the way our Board works could create a perception of conflict of interest.”

Concerning the change in voting for the 13 board members, Thomas wrote,

“It was not an easy change to propose and certainly not an easy one for our board members to approve. They all care deeply about our mission and devote a great deal of thought, time and energy to helping us do our work. So for 13 of them to agree to abstain from a key aspect of their work was difficult to say the least. And yet they did it because they felt it was important for the overall goal of the agency.”

Thomas continued,

“So why did we take this approach? It's simple. We want people to focus on the great work we do, on the groundbreaking research we fund, and the impact we are having on the field of regenerative medicine not just in California but throughout the U.S. and around the world. As long as there are perceptions of conflict of interest hanging over the Board, this will continue to be difficult.”

Thomas said,

“This puts the economic conflicts issue to bed once and for all.”

Loring on Patient Advocates and Their Role at the California Stem Cell Agency

The following statement by stem cell researcher Jeanne Loring was read at the January 23, 2013, meeting of the governing board of the California stem cell agency. Loring is director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, CA.

“I am sorry that I cannot attend this important meeting of the ICOC. I'm in Toronto reviewing stem cell grants for Japan and Canada. I've asked (patient advocate) Don Reed to read my statement.

“I am a California stem cell scientist whose research is funded by the NIH, private foundations, and CIRM. I am the director of one of CIRM's shared laboratories, which has provided formal training in research and ethics to hundreds of young stem cell scientists. My CIRM funding supports the stem cell genomics research that is the main focus of the lab. We have also been funded by CIRM to investigate stem cell therapies for Alzheimer disease and multiple sclerosis. I have leveraged CIRM grant support to obtain funding for studies of autism through the NIH, and for Parkinson's disease from a private foundation.

“The IOM report recommended a number of changes in CIRM's policies. One of these recommendations is of especially great concern to me: the suggestion that patient advocates should have much less influence in CIRM's decisions about what research should be funded.

“Patient advocates are extremely valuable to us researchers. Most of us stem cell researchers had never met a patient advocate- and perhaps not even a patient- before CIRM was founded. In my 20 years of being funded by the NIH, the funding agency never once suggested that I should talk to people who have the disease, or have relatives with a disease that I was receiving funding to study.

“With my first CIRM grant, I started meeting patient advocates, and now I can't imagine pursuing a disease-related research project without them. I've learned a great deal from the advocates on the ICOC, and I greatly enjoy talking with them. They are wonderful sources of knowledge: Jeff Sheehy taught me about HIV/AIDS and patient activism, I learned about Parkinson's disease from Joan Samuelson, autism from John Shestack, and David Serrano-Sewell, Diane Winoker have educated me about MS and ALS.

“Professional research scientists are competitive by nature- a conversation between scientists is often constrained by our secrecy- we need to publish, or perish. But advocates have no such constraints, which makes ICOC meetings more enjoyable and informative than many scientific meetings.

“Patient advocacy has made me a better scientist. Advocacy makes CIRM-funded research breathtakingly relevant and uniquely powerful to change the course of medicine.”

Patient Advocate Reed Defends Patient Advocates on Stem Cell Board

Patient advocate Don Reed, declaring that the Institute of Medicine's (IOM) 17-month study of the $3 billion California stem cell agency is "grossly misguided," this weekend nonetheless said the agency took "the high road" in its response to the study's recommendation.

Reed, of Fremont, Ca., was particularly incensed about the IOM's recommendations concerning patient advocates on the board. The IOM said that none of the board members, including patient advocates, should vote on grant applications secretly in grant review groups. The IOM said their votes should be recorded in public at full board meetings. Other patient advocates would still have seats on the grant review group, under the IOM recommendations. But they would not also be members of the governing board.

The IOM also said that CIRM should also revise its conflict of interest standards to regulate personal conflicts of interest, such as those involving particular diseases and patient advocates. Some members of the CIRM governing board bristled at the recommendation, and the board did not act on it last week.

Last Wednesday, the CIRM board acted to permit board members who are patient advocates to continue to participate in the closed door grant review sessions, but not vote on the grants at that stage. Previously patient advocates had two cuts at applications, one in the grant review group and one at the public board meeting.

Writing on the Daily Kos blog, Reed also said that no real conflicts of interest currently exist on the board, although 90 percent of the $1.7 billion that has awarded has gone to institutions tied to board members.

IOM's Shapiro Wants to See More Changes from California Stem Cell Agency

Additional mainstream media news coverage surfaced last Friday involving the California stem cell agency's response to the blue-ribbon report from the Institute of Medicine(IOM), whose concerns about the agency ranged from conflicts of interest to grant appeals by rejected researchers.

One of the more interesting pieces was done by Stephanie O'Neill of Los Angeles radio station KPCC. To her credit, she contacted the chairman of the IOM panel, Harold Shapiro, for his fresh take on what the stem cell agency's board did on Wednesday.

His comments were somewhat different than those read Wednesday at the CIRM board meeting. On Friday, Shapiro was quoted as saying the board action was “an important first step forward,” but he added a caveat. O'Neill wrote,

“'I’m encouraged by this,' Shapiro told KPCC. 'Presumably in the future they’ll take other steps. But these are steps they could take without any legislative approval and …I think it does respond in a pretty significant way to the spirit of the report.'
“But Shapiro expressed concern that the agency is making only 'small moves' to address a recommendation that CIRM separate operations from oversight. Currently, the ICOC functions 'both as an executor and as an overseer—competing duties that compromise the ICOC’s critical role of providing independent oversight and strategic direction,' according to the December IOM report.
“'But  I do understand… that would be a move that they would have to take over time so we’ll have to wait and see,' Shapiro said.
“Thomas agreed and said that while CIRMs recommendations more clearly define the roles of chairman and president, more refinements will be likely over time.”

From the Los Angeles Times, came a piece from Eryn Brown. Her article was brief and she referred her readers to the California Stem Cell Report for details. Her first paragraph said,

“Changes may be on the way at California’s stem cell funding agency.”

In coverage outside the mainstream media, the Burrill Report carried an article by Daniel Levine. The Burrill Report is produced by Burrill & Co., a San Francisco life sciences financial firm. Levine's straight-forward account was largely based on the CIRM press release and the IOM report.

Two bloggers surfaced with some coverage. UC Davis stem cell researcher Paul Knoepfler, who is a CIRM grantee, called the Thomas plan a “bold one-year experiment” and “biggest development for CIRM in many years.” Knoepfler said,

“I’m still not sure I’m a fan of all of the proposed changes, but I would say the plan is bold and creative.”

On livingbiology.com, an unidentified CIRM grantee carried a few brief items live from the meeting.

Stem Cell Agency Adds Fresh Details to IOM Response

The California stem cell agency today issued a press release touting “dramatic changes” at the agency in response to critical recommendations by the Institute of Medicine.

The press release contained a few more details about the changes than were released in the Power Point presentation yesterday. Here is the text of those details.

• “The 13 Board members appointed from institutions eligible for funding from the stem cell agency, such as those in the University of California system, would no longer vote on any grants brought before the Board but would instead abstain
• “All members of the Board would be able to participate in discussions on applications but only patient advocates and independent members of the Board would be able to vote on funding issues (members would continue to refrain from any discussion of specific applications from their institutions)
• “Patient Advocates would continue to be members of the Grants Working Groups but would not vote on individual applications
• “Programmatic review, aimed at balancing the agency’s portfolio, would take place at public Board meetings where members have a chance to make changes to recommendations from the Grants Working Group
• “Industry involvement would increase, where appropriate, on the Grants Working Group, and also feature in a newly constituted Scientific Advisory Board; the structure and membership of this group is still under discussion
• “Appeals on applications not recommended for funding will be handled by science staff who will evaluate them, determine if they merit further review by the Grants Working Group, and ultimately make recommendations to the Board. Staff will also be allowed to advocate for additional grants not recommended for funding by the Grants Working Group that they believe should be considered in programmatic review
• “The Chair and President would share a division of responsibilities with the President supervising all scientific operations and internal operational responsibilities. In addition the Chief Financial Officer would report to the President. The Chair would handle the ‘external affairs’ aspect of the agency, things such as financial sustainability to raise additional funds, state legislative relations, bond financing, public communications etc.
• “IOM recommendation on the creation of a Scientific Advisory Board to provide counsel on such issues as funding priorities and portfolio strategy will be implemented by staff
• “IOM recommendations on Intellectual Property will be referred to the agency’s IP subcommittee which will review and report back to the full board with options and recommendations
• “IOM recommendations on Sustainability: Chair, working with the President, will develop a plan to address this and present to the Board when ready

California Stem Cell Agency to Pitch Newspaper Editorial Boards

The California stem cell agency is planning an editorial road show with major California newspapers to explain its new plan to deal with the recommendations of the Institute of Medicine(IOM) for major changes at the agency.

In what might be called the kickoff to the campaign, the agency this afternoon issued a press release hailing the plan as making “dramatic changes.”

The agency could have a tough audience. The newspapers editorializing on the subject were unanimously in favor of the IOM recommendations. One said the agency needs to clean up its act. They warned of a loss of public trust along with losing the possibility of continued financial support. (For a sample, see here and here.)

CIRM Chairman J.T. Thomas said during today's meeting that a public relations foray was in the works following board action on his proposals yesterday. He said,

“The opportunity is ripe.”

His comments came after CIRM Director Jeff Sheehy, a UCSF communications manager, urged engaging the editorial boards.

Thomas' plan meets only a portion of the IOM recommendations and sidestepped a call for creating a new majority on the board of independent members. The IOM said “far too many” board members – at least 13 – are tied to institutions that receive money from CIRM. Thomas' plan would have the 13 voluntarily restrain from voting on any grants for any institution.

A compilation by the California Stem Cell Report shows that roughly 90 percent of the $1.7 billion awarded by directors has gone to institutions with links to the directors.  

Nature on the IOM and the California Stem Cell Agency

The journal Nature today said on its web site that the California stem cell agency plans to make a “few changes” in response to a critical report from the Institute of Medicine(IOM).

A short piece by Monya Baker on the agency's response yesterday summarized some of the IOM recommendations and the CIRM response. Baker wrote,

She said,

"Other IOM recommendations were only indirectly addressed by (CIRM Chairman J.T.) Thomas’ plan. The IOM report had stated that the board should restrict itself to an 'oversight' role rather than an 'operational' role. Thomas’s recommendations instead described ways to avoid overlapping duties. His own role as chair is to handle 'external affairs' whereas CIRM’s president will be to handle scientific and internal affairs."

Baker also carried the favorable comments from John M. Simpson of Consumer Watchdog.   

California Stem Cell Agency Overhauling Its Web Site

The governing board of the California stem cell agency adjourned its meeting today at 11:43 A.M. PST following a brief preview of its new web site. The changes are expected to be available online as early as tomorrow. Amy Adams, the agency's communications manager, said the changes are aimed at making the site more accessible and useful to all those interested in stem cell science.

Heart Disease Presentation at Stem Cell Board Meeting

The governing board of the California stem cell agency is hearing a presentation on pediatric heart disease by Deepak Srivastava of the Gladstone Institutes. The formal meeting is scheduled to resume following the presentation. However, there does not appear to be any major business remaining on the agenda.  Nonetheless, the California Stem Cell Report will continue to monitor the meeting for any developments worthy of note. 

Correction

Based on information provided by the California stem cell agency, two items on the California Stem Cell Report today and yesterday carried an incorrect tally, 21-0, on the vote on the plan to deal with recommendations of the Institute of Medicine. The correct figure is 23-0.

More Researchers Eligible for $100 Million Stem Cell Round

Directors of the California stem cell agency today expanded eligibility for the $100 million disease team round to include some earlier recipients in its early translational rounds.

Ellen Feigal, vice president for research and development, said some of those grantees are likely to be ready for more funding as they move closer to clinical trials. She said if they cannot apply in this round, they may have to wait for another year.

Directors agreed that it was important to avoid gaps in funding on successful programs. The RFA could be posted very soon.

Changes in $100 Million Disease Team Round

The disease team three item on the CIRM board's agenda is an alteration of  the original proposal approved in October. The round could total $100 million with awards of up to $20 million each. The agency has not yet posted information on exactly what is to be considered.

Stem Cell Board Begins Meeting

The governing board of the California stem cell agency just began what is expected to be a brief meeting. On the agenda is a proposal for a third disease team round. The agency has already committed $436 million for disease team efforts, which are aimed at translating research into cures.

CIRM Director Pomeroy to Head Lasker Foundation

Claire Pomeroy, one of the original members of the governing board of the California stem cell agency, announced yesterday she has been selected as president of the Lasker Foundation for medical research and will be leaving the board.

In November, Pomeroy said she was resigning from her post as vice chancellor and dean of the medical school at UC Davis to pursue other interests.

Pomeory will assume her new position this spring. Here are links to the Lasker press release and a story in The Sacramento Bee.

Another Big Disease Team Round at California Stem Cell Agency

The California Stem Cell Report will provide live coverage of today's meeting of the governing board of the California stem cell agency. The board is expected to approve another round of its signature disease team grants. So far the agency has approved $436 million, 38 percent of its total funding, for two disease team rounds. The agency has not disclosed on the board agenda any information about the latest round, which could exceed $100 million. Previous disease team rounds have seen awards as high as $20 million each.

Roll Call Vote on the Thomas Plan Dealing with IOM Recommendations

Here is the roll call vote yesterday on the plan to deal with the findings of the Institute of Medicine concerning the California stem cell agency. The vote was 23-0 with one abstention. The board has 29 seats. Not all board members were in attendance, and it is not entirely clear whether all the board members in attendance voted. Among other things, the plan calls for members with links to institutions that could benefit from CIRM awards to voluntarily refrain from voting on any applications for funding – not just those to their institutions. The roll call was provided by a spokesman for the agency.

Yes votes

David Brenner, dean of the UC San Diego medical school.

Anne Marie Duliege , vice president of Affymax

Michael Freidman, CEO City of Hope

Michael Goldberg, executive chairman of Nodality, Inc., and DNAnexus, appointed as executive officer of a commercial life science entity

Sam Hawgood, dean of the UC San Francisco medical school

Steve Juelsgaard, former executive vice president of Genentech, appointed as executive officer of a commercial life science entity

Sherry Lansing, chairwoman of the UC board of regents, appointed as patient advocate

Jacob Levin, assistant vice chancellor, research, UC Irvine, and alternate for Sue Bryant, interim provost at UC Irvine

Bert Lubin, CEO of Childrens Hospital, Oakland

Robert Price, associate vice chancellor for research, political science professor, alternate for the UC Berkeley chancellor

Francisco Prieto, Sacramento physician and patient advocate member of the board

Robert Quint, San Jose physician and patient advocate member

Duane Roth, San Diego businessman, appointed as executive officer of a commercial life science entity

Joan Samuelson, patient advocate member

Jeff Sheehy, patient advocate member

Jon Shestack, patient advocate member

Os Steward, patient advocate member and head of the Reeve-Irvine Research Center at UC Irvine

Jonathan Thomas, chairman of the board and Los Angeles bond financier

Art Torres, patient advocate member

Kristiina Vuori, interim CEO of Sanford Burnham Research Institute

Diane Winokur, patient advocate member
Claire Pomeroy, dean of the UC Davis medical school
Shlomo Melmed, senior vice president for academic affairs, Cedars Sinai

Abstaining

Michael Marletta, CEO of Scripps Research

(Editor's note: Based on information provided by CIRM, an earlier version of this item incorrectly reported that the vote was 21-0. It also contained errors on three names. All have been corrected. Thanks for the heads up on the misspellings from a board member who will remain unnamed.)

Meager, Meager Coverage of Yesterday's IOM-Stem Cell Meeting

The $3 billion California stem cell agency seemed all but invisible this morning in terms of mainstream media coverage.

Only one major outlet reported on the watershed events yesterday at the CIRM governing board meeting at the Claremont Hotel in Oakland – at least from what our Internet searches show.

The piece was written by Bradley Fikes in the San Diego U-T, the dominant daily newspaper in that area, which is a major biotech center. The major media in the San Francisco Bay area, home to the stem cell agency and also a biotech center, were absent from the coverage.

Fikes wrote a straight forward account of the meeting, saying that the governing board voted “ to accept in concept proposed changes to reduce conflicts of interest on the agency's governing committee.”

Fikes wrote the story based on the audiocast of the meeting. He probably would not have written his daily piece without the availability of the audiocast. 

Some of those connected with the stem cell agency often wonder about the lack of mainstream coverage of its doings, particularly the lack of favorable coverage.

Much of it has to do with the shriveled state of the media business, which is understaffed and overworked compared to 15 years ago. Specialized science reporters are all but an extinct species. Also, the mainstream media has traditionally ignored the affairs of most state agencies.

Speaking as a former editor at a major Northern California newspaper, I would not have sent a reporter to cover this week's two-day CIRM board meetings. It would have consumed too much valuable time with little likelihood of a major story, especially when weighed against other story possibilities. There was no guarantee that the board would have even acted. The events and their significance could be better handled in a roundup story later with more perspective, perhaps keying on the board's meeting in March, where details of yesterday's action will be fleshed out. The fact is that many, very important events occur within state government every day that never receive media attention. Some don't even see the light of day until a catastrophe occurs.

All of this may be deplorable in the eyes in stem cell agency backers and others, but it is the reality of today's news business.  

Reaction to IOM: California Stem Cell Directors Approve Plan on Conflicts of Interest and More

Directors of the $3 billion California stem cell agency today approved a far-reaching plan aimed at resolving long-standing conflict of interest issues involving the agency's governing board and also at helping to maintain credibility with the public.

Jonathan Thomas
CIRM photo

The framework of the proposal by CIRM Chairman J.T. Thomas moved forward on a 23-0 vote with one abstention. He laid out the plan in response to sweeping recommendations from a blue-ribbon study by the Institute of Medicine. Details will be worked out and come back to the board in March. 

Acknowledging that many board members were not pleased with the IOM criticism of the agency, Thomas said, 

“This is one of those times that we must move forward and compromise.” 

He said issues such conflicts of interest have “stolen focus” from the good scientific work that the agency has funded.

Thomas was reacting to the $700,000 IOM study commissioned by CIRM governing board. The IOM recommendations called for removing conflict of interest problems, cleaning up a troubling dual-executive arrangement and fundamentally changing the nature of the governing board. The IOM proposals would strip the board of its ability to approve individual grants, greatly strengthen the role of the agency's president, significantly alter the role of patient advocates on the governing board and engage the biotech industry more vigorously.

Thomas' plan, which would be put in place for up to a one-year trial period, would not do all that the IOM wanted, but would move strongly in that direction.

State Controller John Chiang, chairman of the only state entity with financial oversight over CIRM, endorsed most of the proposal, said deputy controller Ruth Holton-Hodson. She told CIRM directors that Thomas' plan was thoughtful and positive, although Chiang did not support continued involvement of the chairman in day-to-day operations.

The Thomas plan, which would not require legislative approval, would:

• Have 13 members of the 29-member board refrain from voting on specific grant applications. The 13 would be from institutions that could benefit from CIRM grants. They would be allowed to participate in discussions. Thomas said this would deal with financial conflict of interest questions. 
• Increase industry participation of industry in grant application review and step up business involvement internally at CIRM, including development of RFAs.
• Redirect all scientific appeals to staff to evaluate for possible re-review before they go to the full board.
• Move “programmatic” review of grants to public sessions of the full board instead of being held behind closed doors during grant review sessions. Patient advocate directors now sitting on the grant review group would no longer be allowed to vote during the closed-door review sessions, but they could participate in the discussion.

It appears, however, that the Thomas plan would do little to deal with the dual-executive problems identified by the IOM.

Consumer Watchdog's John M. Simpson, a long observer of the stem cell agency, welcomed the response by CIRM. Writing on his blog, Simpson said,

 "It looks like the message is finally getting through to California's stem cell agency board....
Part of what is driving the new approach is the realization that CIRM will need to find a new source of funding -- possibly going back to the voters -- if it is to continue.  As Thomas told the board today, 'If we don't have credibility, we won't have a chance of sustaining the agency.'"

During the lengthy debate this afternoon, one director after another said they did not agree with all that the IOM had to say, but said maintaining credibility and trust was the key to the sustainability of the organization.

CIRM will run out of money for new grants in less than four years. Thomas said he is working on a plan to continue the agency's effort into the future. Details of that will be disclosed later, he said.

(Editor's note: An earlier version of this item, based on incorrect information from CIRM, said the vote was 21-0. The correct figure is 23-0.)

California Stem Cell Agency Directors Approve Changes to Meet IOM Recommendations

The board of the California stem cell agency has adjourning following approval of the Thomas plan to deal with recommendations of the Institute of Medicine for changes at the agency. More details shortly.

Vote Nearing on Thomas Response to IOM Recommendations

The governing board of the California stem cell agency appears to be heading for a vote on the Thomas IOM plan, which he has agreed to place on a one-year test timetable. The plan is being described as a "framework" with details to be worked out. The proposal would be fleshed out and come back to the board in March for later action. Several board members have raised questions about the details. But Thomas and other supporters say those will have to be worked out.

Consumer Watchdog Welcomes Changes at Stem Cell Agency

Consumer Watchdog's John M. Simpson today welcomed the response by CIRM 

Chairman J.T. Thomas to address the recommendations for sweeping changes at the California stem cell agency. 

Writing on his blog, Simpson, a longtime observer of the agency, said, 

"It looks like the message is finally getting through to California's stem cell agency board....
"Part of what is driving the new approach is the realization that CIRM will need to find a new source of funding -- possibly going back to the voters -- if it is to continue.  As Thomas told the board today, "If we don't have credibility, we won't have a chance of sustaining the agency."

Thomas' IOM Plan Receiving Generally Positive Response

So far,  many of the directors of the $3 billion California stem cell agency today seem to be endorsing the plan proposed by Chairman J.T. Thomas to meet the sweeping recommendations by  the Institute of Medicine.

Several members stressed the need to remove the perception of conflicts of interest on the board, as identified by Institute of Medicine and other studies of the stem cell agency.  Concerns about conflicts of interest go back as far as the election in 2004 when the plan to create the stem cell agency was presented to the voters of California.

Director Sherry Lansing, who is chair of the UC Board of Regents, said "we can't fight" the perceptions any more. She said the board needed to move forward and control its own destiny instead of having to deal with possible legislative changes. Continued perception issues "will harm our work," she said.

However, a couple of other members expressed some dissent.

Among other things, Thomas' plan would require 13 members of the board not to vote on individual grants, although they could take part in debate on them. The 13 are members who are linked to institutions that are likely recipients of CIRM awards. All of the changes proposed by Thomas could be done without legislative action, he said. Thomas also said that chairman of the IOM study panel endorsed his plan, saying it would serve the best interests of the people of California.

According to compilations by the California Stem Cell Report, about 90 percent of the $1.7 billion awarded by CIRM has gone to institutions with ties to members of the CIRM board.

Here is a link to the Power Point presentation of Thomas' plan.

Thomas' Plan to Meet the the Recommendations of the IOM

Jonathan Thomas, chairman of the California stem cell agency, presented the following plan today to the governing board of the agency to deal with recommendations of the Institute of Medicine. 

  IOM proposal by the chairman of the California stem cell agency by  

Thomas Presents Plan On IOM Recommendations

Directors of the California stem cell are engaged in an intense discussion over a plan by CIRM Chairman Jonathan Thomas to deal with the recommendations from the Institute of Medicine. Thomas said the detailed proposal would require 13 board members to voluntarily not vote on grant applications. The agency says it will post Thomas' plans shortly on its web site. Most of the board members speaking so far have endorsed the plan.

CIRM Directors Resume Meeting

The California stem cell agency board has just resumed its meeting on the Institute of Medicine report with the swearing-in of members who were just reappointed to their posts.

CIRM Board Member Cites Valuable Role of Patient Advocates

Jeff Sheehy, a patient advocate member of the governing board of the California stem cell agency, last month said the Institute of Medicine was recommending what amounted to "defenestration" of the 10 patient advocate members on the board.

Following a staff presentation this morning on the scientific progress of the agency, Sheehy took the opportunity to point out that several of the programs highlighted were only underway because of efforts patient advocates or appeals by rejected applicants.

Sheehy, who is vice chairman of the CIRM grant review group, said "programmatic" reasons advanced by patient adovocates led to the group's approval of two of the programs. Two more of the highlighted awards were rejected by grant reviewers but only approved by the full board after the applicants appealed using the agency's extraordinary petition process.

The IOM has recommended that the petitions be eliminated because of the threat they pose to the scientific peer review process. It has also recommended that the board not vote on individual grants -- only a slate approved by reviewers. The IOM additionally has recommended major changes in the role of patient advocates on the board.

Lunch for Stem Cell Directors; IOM Coming up in About an Hour

Directors of the California stem cell agency have taken a lunch break. They broke at 12:04 p.m. PST and will return at about 1:15 p.m. PST and begin discussion of the Institute of Medicine report. Upcoming is an item on a comment by one director about the value of patient advocates in moving grant applications forward.

Stem Cell Directors Discussing CIRM's Science Program

The staff of the California stem cell agency has concluded a more than one hour briefing on the agency's science portfolio. Directors are now beginning discussion of the staff presentation, which serves as a basis for future endeavors of the agency and also a basis for building support for the $3 billion.

Review of CIRM Science Program Continuing

The staff of the California stem cell agency is continuing with its overview of what the agency has done with the $1.7 billion it has awarded in terms of science. Thirty-eight percent of the amount has gone for translational research, efforts at turning basic research into a product. Here are links to a document on the science program and the Power Point presentations. 

California Stem Cell Agency Directors Begin IOM Meeting

The board of the California stem cell agency has begun its meeting today dealing with the recommendations of the Institute of Medicine. The first order of business is a staff report on the scientific portfolio of the agency. The nitty gritty of the IOM report is scheduled to taken up about 1:15 p.m. PST.

Inside the Grant Review Process at the California Stem Cell Agency

One of the major issues today involving the California stem cell agency and the Institute of Medicine revolves around the grant review process, appeals and conflicts of interest.

The agency has prepared a presentation of how it perceives the process. The Institute of Medicine has also described the review process. Both descriptions offer different sorts of insights into the procedures.

We are offering both characterizations. Both have at least one error and other limits. The IOM, for instance, says grant applicants who file extraordinary petitions are invited by CIRM to make public presentations to the board. That is not the case.

CIRM's presentation refers to a second tier category for applications, a category that has not been used for some time by the agency. The agency also says that it provides to the public in advance of board meetings statistics on the spread and deviation of reviewer scores on applications. That is not the case. The material, a key board tool for evaluating appeals, has generally not been available to the public until the day of the meeting, if then. Sometimes it has only been available via a Power Point presentation on a screen at the meeting. The CIRM slide on executive sessions says that board members do not discuss merits of an application in executive session. That assertion is marginal at best. Last September, statements by the chairman of the board clearly indicated that such a discussion occurred during an executive session. From our attendance at other meetings, it seems abundantly clear that discussions do occur in executive session.

We have queried the agency concerning the statements in the grant review presentation document.

Readers should also be aware that grant reviewers make the de facto decisions on grants, although the board has final legal authority. The board has almost never rejected a grant approved by reviewers. The board also goes along with reviewers on the vast majority of applications that are rejected.  The board, however, does pick a few applications not favored by reviewers in each round and approves them. 

That said, both of descriptions are helpful in understanding the process. Here is a link to the text of the IOM description. The CIRM description is embedded in a document on its web site and can be found as exhibition B.

IOM Description of CIRM Grant Review Process

Here is the text of the Institute of Medicine's description of how the grant review process works at California stem cell agency. You can find CIRM's version as exhibit B in this document.

"CIRM staff are available to potential applicants to discuss ideas and to answer questions about published RFAs and the conformity of a particular proposal to the goals of announced programs. From responses to a questionnaire submitted by the committee to the California stem cell scientific community, 4 it appears that views on discussions of this type vary, with some individuals being highly appreciative of these preliminary discussions and others finding the CIRM staff less accessible (IOM, 2012d). The committee agrees that having a system for communicating with potential applicants early in the process is important, in particular to ensure that neither applicants nor CIRM staff are spending large amounts of time writing or assessing proposals that are not in keeping with the goals of any particular RFA. The committee also suggests that CIRM continue making its scientific staff available to potential applicants and working with this constituency to maximize the effectiveness of this aspect of the grant submission process.

"CIRM staff recognized that the number of applications that would potentially be received for a given RFA could overwhelm the Institute’s ability to review each rigorously for scientific merit. Accordingly, during its early years, CIRM restricted the number of applications that would be accepted from any one institution in response to a particular RFA. The reasoning was that doing so would limit the overall number of applications, making the review process manageable while guaranteeing that applications would represent the scientific communities at a wide range of California institutions. This was especially important given that CIRM’s enabling legislation limited administrative expenditures, requiring that the process for grant-making decisions be streamlined. However, there was considerable pushback from potential grantees, as it was thought that some individuals, in particular junior investigators or those new to stem cell biology, were at a disadvantage in competing with colleagues at their home institutions for the right to submit a proposal and hence had limited access to possible CIRM support.

"To address this concern while keeping the number of proposals sent for full review manageable, CIRM established a pre-application procedure and eliminated the restriction on the number of applications that could be submitted from any single institution (CIRM, 2011d). The preapplication procedure is similar to a process used by a number of private foundations that provide support for biomedical research. Applicants are asked to provide a shortened version of their proposal through the CIRM website. CIRM staff evaluate these shortened proposals to ensure that they are in keeping with the RFA. Those deemed responsive to the RFA are then sent to three outside reviewers, who are also provided the RFA. Each reviewer is asked to evaluate the preapplication, indicating whether it should definitely, possibly, or definitely not be invited as a full proposal. Additionally, each reviewer is asked to identify proposals that are among the two to three best in the group being evaluated by that reviewer (each reviewer typically is given 10-25 pre-applications to consider). No written critique is requested of the evaluators. Using these initial external evaluations, CIRM staff determine which applicants will be invited to submit full proposals. Once invited, proposals must be based on the pre-application proposal that was submitted. There is no appeal process for pre-applications that are not invited for a full proposal submission (CIRM, 2011e).

"After the pre-application process was piloted, applicants, reviewers, CIRM staff, and the ICOC board members were surveyed regarding its acceptability (CIRM, 2011e). As might be expected, applicants often expressed frustration that there was no feedback on why their pre-application was not selected to move forward. Additionally, in responses to the committee’s questionnaire 5 , some principal investigators raised concern about whether a short proposal contains sufficient detail for an informed review (IOM, 2012d). On balance, however, there appeared to be overwhelming support for the pre-application process, especially in comparison with the previous model whereby there was a limit on the number of applications that could be submitted from any single institution (CIRM, 2011e). The committee agrees that, despite its limitations, the current preapplication procedure opens up the opportunity for CIRM funding to a broader cohort of investigators and is, in principle, an appropriate process. The committee recognizes the tension between providing applicants as much information as possible and not overburdening reviewers, and suggests that CIRM consider ways of offering applicants more information on the shortcomings perceived in preapplications that were not selected for further consideration.

"The Scientific and Medical Research Funding Working Group, designated in most CIRM materials as the Grants Working Group (GWG), is the entity charged with reviewing scientific proposals and making recommendations to the ICOC (the CIRM governing board) with respect to those that should be funded.

"The GWG is appointed by the ICOC and consists of 23 members, including the chair of the ICOC, 7 of the 10 ICOC patient advocates, and 15 non-California scientists known for their expertise in stem cell biology (CIRM, 2009f, 2012g). The 15 scientists are selected based on the particulars of the individual RFAs and are drawn from a pool of more than 150 individuals chosen by CIRM as highly qualified to review proposals. Participation of these experts, none of whom, as non-Californians, are eligible for CIRM funding and stand to gain directly from CIRM, is instrumental in providing the rigorous scientific review required for making funding decisions. The success CIRM has had in commissioning outstanding review committees for each of its RFAs is a testament both to the Institute’s stature in the eyes of the stem cell community and the willingness of stem cell scientists outside of California to contribute their time and effort to facilitate the work of their California colleagues.

"Full proposals received by CIRM by the RFA deadline are entered into the CIRM database, and all GWG members assigned to this review cycle declare any conflicts of interest with any of the applications (CIRM, 2009g). Any GWG member in conflict for a particular application is recused during discussions, scoring, and final voting. The GWG members are then assigned applications for which no conflict exists based on their unique expertise. Typically, three external scientists review each application. The GWG can call on additional specialist reviewers as needed if its own expertise is insufficient to evaluate the science in any individual application adequately. Prior to the GWG’s face-to-face meeting, each reviewer and ad hoc specialist submits a scientific score (1-100, with 100 being best) and a written critique for each assigned application. A meeting of the GWG is then announced on the CIRM website. This meeting starts with a session open to the public, during which GWG business is conducted. The GWG then meets in closed session for a two-stage review of the applications (CIRM, 2011g).

"The first stage of the review is scientific in nature, led by the chair of the GWG (an external scientist member appointed to this role by the ICOC). The assigned reviewers declare their scores for the application being discussed and briefly summarize the basis for their recommendations. This is followed by full discussion of the application by GWG members, ending with the assigned reviewers suggesting revised scores based on the discussion. Each scientific member of the GWG not in conflict with that application then submits a final scientific score. Although ad hoc specialist reviewers can suggest scores in their written evaluations and, if present, during the discussion, only GWG members can submit a final score. The final scientific score is the arithmetic mean of the reviewers’ scores. If there is a wide divergence in scores with a sizable proportion (greater than 35 percent) of the GWG being in disagreement with the majority view, a minority report is forwarded to the ICOC along with the final score (CIRM, 2011g).

"The next stage is the programmatic review, chaired by one of the patient advocate members of the GWG appointed to this position by the ICOC (CIRM, 2011g). The purpose of this review is to evaluate all of the applications taking into account not only their scientific scores but also the overall purpose of the RFA, with the goal of segregating the applications into three tiers— recommended, provisionally recommended, or not recommended for funding. This process has two steps. First, a histogram of the scores of all of the applications is generated. Of note, at this stage the applications are deidentified, and only the scores are revealed. The GWG examines this histogram and identifies natural breaks to divide the applications into the three tiers based on their scores. Next, the applications are identified so that the scientific score (and tier) of each is made known. GWG members (except those with conflicts, who leave the room) begin a discussion to determine whether any of the applications should be moved from one tier to another in an effort to achieve a balanced portfolio representing a spectrum of priority disease areas, scientific approaches, innovation, and so forth. For an application to be moved from one tier to another, a majority vote of the GWG is required; all members of the GWG not in conflict (scientists and patient advocates) participate in this vote. Once the GWG is satisfied with the final ranking of proposals, a final vote is taken, and the rank order is proposed to the ICOC for approval. For each application, in addition to its final ranking, the scientific score voted by the scientists on the GWG is provided to the ICOC (CIRM, 2011g; IOM, 2012e).

"The ICOC makes funding decisions at a meeting scheduled and publicized in advance. As with other ICOC agenda items, deliberations on the funding of applications begin in a session that is open to the public. ICOC board members in conflict with any particular application are recused from both this public discussion and any subsequent private deliberations. Prior to the ICOC meeting, summary information about each application is available on the CIRM website, including how that particular application ranked relative to the others and its tier designation.

"Applications are redacted, however, to remove information that would identify applicants or institutions. Individual applicants are aware of how their proposal scored and how likely it is to be funded, and have the opportunity to make an “extraordinary petition” to the ICOC. Any ICOC board member may request that the petition be heard. In such cases, petitioners are invited to the ICOC meeting to explain why they believe the assigned score and priority ranking are not appropriate.(California Stem Cell Report note: The preceding sentence is in error. Petitioners are not invited to appear. In fact, some have not understood their right to appear. Others do not even understand that they can file a petition.)

"The ICOC takes this information (the petitions) into consideration as it deliberates about the final ranking of applications. If it is necessary to discuss proprietary information, the ICOC may meet in closed session before a final vote is taken on which applications will be funded. As a result of its private and public deliberations, the ICOC may move applications from one tier to another before taking a final vote, after which applicants are notified about funding decisions. Examination of ICOC records indicates that the shifting of applications from one tier to another does occur. For example, as of October 22, 2012, 62 extraordinary petitions were heard by the ICOC, of which 20 (32 percent) were successfully funded (CIRM, 2012h). While most of this shifting is between adjacent tiers, there have been cases in which applications have been moved from tier 3 to tier 1 (CIRM, 2011g; IOM, 2012e); this has occurred with applications for major programs with large budgets. As discussed in greater detail below, the committee is troubled by the extraordinary petition mechanism and suggests that this practice be eliminated. The committee recognizes that CIRM has recently initiated a self-study regarding all aspects of extraordinary petitions."  

The IOM and CIRM: Live Coverage of Today's Meeting

The California Stem Cell Report will provide live coverage of today's and tomorrow's key meetings of the governing board of the $3 billion California stem cell agency as it discusses action on the far-reaching recommendations of the Institute of Medicine. Stories will be filed as warranted. The meeting is scheduled to begin in Berkeley, Ca., at 10:30 a.m. PST today and 9 a.m. PST tomorrow.

Texas and California: Conflicts, Research Funding and Controversy

As directors of the $3 billion California stem cell agency begin a critical meeting today that involves both its future and conflicts of interest, a move is afoot in Texas to cut off funding for a similar research organization embroiled in controversy over its grant review process and favoritism.

The Texas Tribune in Austin yesterday reported that a Republican legislator has introduced a measure that could ending funding for the $3 billion Cancer Prevention and Research Institute in that state. Both the Texas organization and the California agency rely on money (bonds) that is borrowed by their state governments. Other separate kmoves are also underway in the Texas legislature to make major changes in the research funding.

The Texas agency has been involved in controversy over its grant review procedures for months. The issues have led to mass resignations of its reviewers and persistent public turmoil. In California last fall, CIRM President Alan Trounson warned about the implications of the Texas flap for his agency. Later in December, the blue-ribbon report by the Institute of Medicine about CIRM said the Texas situation “illustrates the importance of rigorous scientific review free from inherent or perceived conflict and the consequences when these boundaries appear to be breached.”

The IOM study of CIRM said “far too many” of the agency's directors are linked to organizations that have received CIRM grants. A compilation by the California Stem Cell Report shows that about 90 percent of the $1.7 billion awarded by the governing board have gone to institutions with ties to directors.

The IOM inquiry, commissioned by CIRM at a cost of $700,000, recommended that a majority on the 29-member CIRM governing board consist of "independent" members. Currently the board has no “independent” members. They come from legal classifications that range from patient advocate to five “executive officers” from five different University of California campuses. Industry is only marginally directly represented on the board. The specific classifications can be found in this CIRM document.

Today's meeting begins at 10:30 a.m. PST in Berkeley. The California Stem Cell Report will provide live coverage of the sessions today and tomorrow via the audiocast that is available to the public. Directions for listening to the audiocast can be found on the meeting agenda. 

California Stem Cell Agency: IP and Sustainability Off the Table Tomorrow

The California stem cell agency says that tomorrow's meeting regarding the sweeping changes recommended by the Institute of Medicine (IOM) will not include discussion of intellectual property issues or proposals for the “sustainability” of the $3 billion enterprise.

In a memo to the governing board of the agency posted on its web site today, James Harrison, outside counsel to the board, said,

“The chairman (Jonathan Thomas) has conveyed his view that CIRM should maintain its existing policies regarding revenue sharing, pricing, and access. In addition, chairman Thomas is working on proposals to address the IOM committee’s recommendations regarding a sustainability platform, but it would be premature to discuss these proposals at this time. Therefore, we do not intend to devote significant time to either the intellectual property or sustainability platform recommendations. Instead, we hope to focus the discussion on governance issues and the application review process.”

The CIRM board begins a critical, two-day session tomorrow in Berkeley to consider the IOM's recommendations, which met initial resistance last month from a number of the agency's 29 board members. The recommendations would make major changes in the board and would mean some members would lose their seats, if the proposals were adopted without change.

The IOM also said that the board needs to overhaul its conflict of interest standards, declaring that “far too many” board members are tied to organizations that benefit from CIRM's largess. The agency has long been a target of criticism that it has conflicts of interests that were built in by Prop. 71, the ballot measure that created the program. Roughly 90 percent of the $1.7 billion that the board has awarded has gone to institutions that are linked to members of the agency's governing board, according to compilations by the California Stem Cell Report.

Arthur Caplan, a prominent medical ethicist at New York University, says that the IOM has concluded that CIRM's grant award process is “insular and somewhat incestuous.”

Harrison's document was long on the positive aspects of the blue-ribbon IOM study, which CIRM is paying for at a cost of $700,000. It was commissioned by the board in 2010 with the intent that it would be a springboard to another multi-billion dollar state bond measure, which requires voter approval. CIRM operates on money that the state borrows (bonds). The interest on the bonds will bring the total cost to taxpayers to roughly $6 billion. The financial arrangement is unusual for research funding and differs from federal funding, which is not based on borrowed cash. The CIRM bond money, however, will run out in less than four years. 

Harrison cited 10 points in which the IOM had praise for CIRM, points that few would differ with in any major way, even prior to the IOM study. Some might quibble, however, with a few of Harrison's effusive adjectives.

Significantly, Harrison did not present a fresh legal analysis that might have raised the possibility of constitutional objections to the IOM proposals. A memo from Harrison in 2009 was used by then CIRM Chairman Robert Klein to box in the board in connection with other, similar suggestions for changes at the agency. 

Harrison also disclosed that board's intellectual property (IP)subcommittee will examine the IOM's proposals on IP later and make recommendations. The IOM suggested, among other things, that CIRM modify its policies to bring them in line with federal law, which is not without its own controversies.

Tomorrow's session will be covered live by the California Stem Cell Report via CIRM's audiocast, which is available to the public, and we will file stories as warranted. The meeting begins at 10:30 a.m. PST. Directions for dialing into the audiocast can be found on the agenda for the meeting.

'Insular and Somewhat Incestuous:' California Stem Cell Agency Grant Review Process

How can the Institute of Medicine's (IOM) conclusion about the grant review process at the $3 billion California stem cell agency be summarized? “Insular and somewhat incestuous” is the way one nationally known expert on medical ethics describes it.

The characterization was offered by Arthur Caplan, director of NYU Langone Medical Center’s Division of Medical Ethics, in a piece in the San Diego U-T, the dominant newspaper in that Southern California hotbed of biotech research.

In the article posted online late yesterday by reporter Bradley Fikes, Caplan said,

“Rather than getting into an ongoing debate about the adequacy of the existing peer review process, it should suffice to say that a distinguished, independent review found the current process to be insular and somewhat incestuous.” 

Fikes also reported,

"Michael Kalichman, director of the Center for Ethics in Science and Technology in San Diego, said the IOM report offers 'thoughtful' and constructive criticism. 

"'As funding becomes more limited, and this is likely, it will be necessary to make hard choices about what is and is not worth funding,' Kalichman said. 'Even if the decisions made are truly the best possible decisions, there is a high risk of the perception that particular voices represented on the ICOC (the agency's governing board) are heard better than those who are not represented.'”

Fikes' article is a preview of Wednesday's and Thursday's meetings in Berkeley during which the 29 directors of the agency are scheduled to discuss the IOM's $700,000 report, paid for by the agency itself, and determine a course of action.

Fikes' piece provided the first public IOM comment from Robert Klein, the former chairman of the stem cell agency. Klein directed the writing of the 10,000-word ballot initiative that created the stem cell agency eight years ago. He additionally crafted good portions of the measure including detailed qualifications for the chairman that appeared to restrict the choice to only one person in the state. Klein also lobbied his former colleagues vigorously and successfully last year for $40 million for StemCells, Inc., of Newark, Ca., 

Fikes reported that Klein  “said fears that grants would be awarded by favoritism have been disproved by experience. And patient advocates on the committee cooperate instead of compete, because research on one disease often proves useful for other diseases.”

One of the StemCells, Inc., applications was rejected twice by reviewers, whose actions were ultimately overridden by the board. Last year saw a record level of lobbying involving reviewer-rejected applications and patient advocates who sought to overturn decisions. At one meeting last fall, some board members expressed their displeasure with “arm-twisting,” lobbying and “emotionally charged presentations.” The board is also working on a new policy that would restrict “ex parte communications” – contact outside public board meetings – with board members.

The IOM additionally recommended that a majority of the agency's governing board consist of independent members. Currently the board has many conflicts of interest built in by Prop. 71, the measure that created the agency. About 90 percent of the $1.7 billion that the board has awarded as gone to institutions connected to persons who sit on the board, according to compilations by the California Stem Cell Report. Board members are barred from voting on applications from their institutions, but they set the agenda for what type of research is to be pursued and also approve detailed concepts of proposed requests for grant applications.

Fikes quoted UC Davis stem cell researcher Paul Knoepfler on the IOM recommendations for changes in composition of the board. Knoepfler said,

“Who exactly would be qualified to be on such a IOM-approved board and why should we Californians (and stem cell scientists and other stakeholders) trust them to be informed and passionate about stem cell research the way the current ICOC(the agency governing board) has shown itself to be over and over again? The IOM provides no answer to this question.”

StemCells, Inc., Still Looking for $40 Million from California Stem Cell Agency

Remember StemCells, Inc., and the $40 million it was awarded by the California stem cell agency.

The Newark, Ca., firm, founded by eminent Stanford researcher Irv Weissman, received an award of $20 million last July and then again in September. Nearly five months later, however, the stem cell agency has yet to cut a check for the company, a spokesman for the agency told the California Stem Cell Report in response to a query.

The hang-up is the $40 million in matching funds that the company promised the agency. The stem cell agency has yet to be satisfied that StemCells, Inc., can actually produce the match, although the spokesman did not offer details.

The StemCells, Inc., awards were unusual in a number of ways. It was the first time that former CIRM Chairman Robert Klein lobbied the CIRM governing board on behalf of a company(see here and here). It was the first time that the governing board approved an application that had been rejected twice by grant reviewers. It was the first time that the board said explicitly in a public session that it wanted proof of the matching funds as a condition of the award.

It was the first time that a CIRM award to a company received a careful and critical scrutiny from a major California newspaper. Michael Hiltzik, a Pulitzer Prize-winning business columnist and author, wrote in October in the Los Angeles Times that the award was “redolent of cronyism.” He referred particularly to longstanding ties between Klein and Weissman.

The CIRM board vote on the StemCells, Inc., grant in September was 7-5, which amounted to 12 out of 29 members of the board.

In December, a blue-ribbon panel of the Institute of Medicine (IOM) recommended that the agency tighten its conflict of interest standards to avoid such perceptions as have been generated by the StemCells, Inc., awards. The IOM said,

“(C)om­peting personal and professional interests com­promise the perceived independence of the (governing board), introduce potential bias into the board’s decision making, and threaten to undermine confidence in the board.”

Concerns about conflicts of interest have long been of concern to observers of the stem cell agency for years. Indeed, the prestigious journal Nature in 2008 warned of "cronyism" at the $3 billion research enterprise.

Stem Cell Agency Chair Pressing for Consensus on IOM Recommendations

The chairman of the $3 billion California stem cell agency, Jonathan Thomas, yesterday outlined how he intends to proceed next week when the agency's governing board considers the far-reaching recommendations of a blue-ribbon Institute of Medicine panel.

Writing on the agency's blog, Thomas said,

“While some of the IOM’s recommendations are administrative in nature and can be implemented, others are much more complex and would require changes in (governing) board policy or legislative changes.” 

Jonathan Thomas, chairman of CIRM governing board at far right. Art
Torres (center), co-vice chair and former state Democratic party chairman,
who would  play key role in dealing with lawmakers. Robert Klein is at the
 left in this 2011 meeting, Klein's last as chairman of the agency and the one
 in which Thomas was elected chairman. 

He continued,

“My goal is to strive to reach consensus on a course of action on the 23rd. However, if the board isn’t able to choose a course of action at this time we will continue the conversation and bring it up at future board meetings until we reach agreement.”

It is worth noting that Thomas did not mention the possibility of having to ask the people of California to amend the state constitution, which would require a statewide election. Opponents to change at the agency have used that possibility to discourage action. (See here and here.) An election would be costly, politically difficult and could open the door to additional unwelcome changes at the eight-year-old research enterprise.

Thomas' desire for a consensus among the 29 board members – instead of a simple majority – could be a stumbling block as the board becomes snarled internally, perhaps for months or more. The board normally meets only about once a month and has a full slate of regular business on those occasions. The agency will run out of money for new grants in less than four years, and action on the IOM recommendations seems a necessary prelude to winning continued financial support.

While four years would appear to an ample period of time, making the sort of changes the IOM recommends would require legislative action, which probably would take a minimum of a year. Timing is important as well. The current leaders in the state Senate and Assembly will be termed out in 2014. Starting all over with novice leadership, changes in key committee chairmanships and so forth would make the task even more difficult. Then there is the need to address strategies for continued financial support. Should the agency seek a new statewide bond measure (the current funding mechanism)? If so campaign committees need to be formed, electoral strategies planned and tested and tens of millions of dollars raised for campaign expenses. If private funds instead are to be raised to the tune of hundreds of millions of dollars(the agency spends about $300 million a year), such an effort would also require considerable time. To keep the funding pipeline full, all of this should be completed well before the money runs out in 2017.

Dilly-dallying this year in drawn-out, fruitless debate over the IOM proposals would be an unfortunate beginning should CIRM directors actually want to continue the existence of the organization.

In his blog item, Thomas sounded this final note.

“It’s likely the debate will be passionate – everyone involved in this work cares deeply about it – and there will undoubtedly be disagreements, but ultimately we all share the same goal, a desire to make sure that whatever we decide helps make the stem cell agency even stronger and more effective, and is in the best interests of the people of California.”

UC Davis Stem Cell Researcher: 'Ivory Tower' IOM Recommendations Harmful to California Stem Cell Agency

The $3 billion California stem cell agency has funded in the neighborhood of 500 to 600 scientists and institutions, reviving and starting careers and stimulating construction of $1 billion in new research labs around the state.

None of those recipients, as far as we know, has come forward to comment publicly on the sweeping recommendations by Institute of Medicine for changes at the agency. Until today, that is.

UC Davis researcher Paul Knoepfler, who may be the only stem cell scientist in the United States with a stem cell blog, weighed in with his thoughts today, which do not align with those of the blue-ribbon IOM panel.

“Harmful” is one word that Knoepfler, who is a stem cell agency grant recipient,  used to describe the recommendations. He predicted “extremely negative repercussions” that “would actually make CIRM less effective and less responsive to patients and California citizens.”

He wrote that the IOM report, which will come before stem cell agency governing board next week “...seems more like an ivory tower intellectual exercise than an operative, realistic guide to a dynamic agency that must operate in the real world.”

He defended the CIRM governing board, which came under fire from the IOM for conflicts of interest. Institutions linked to board members have received about 90 percent of the $1.7 billion that the board has awarded, according to compilations by the California Stem Cell Report. The IOM said,

“Far too many board mem­bers represent organizations that receive CIRM funding or benefit from that funding. These com­peting personal and professional interests com­promise the perceived independence of the ICOC, introduce potential bias into the board’s decision making, and threaten to undermine confidence in the board."

Knoepfler said,

“(The) IOM itself admits there is no evidence that any conflicts of interest have ever guided (the agency's governing board) decisions. Not one example.”

Knoepfler also wrote,

“Interestingly, highlighting the extremely sensitive nature of this issue, while I’ve been talking with many bigwigs about this, at this point no one is wiling to go on the record with an opinion about it except one courageous soul, Don Reed (see his piece here).”

There is a reason for that. The IOM is the most prestigious organization of its sort. Its studies are described as the gold standard. And it has a rareified membership that many scientists seek to join. So few are ready to give the organization a smack on the nose. Likewise, California researchers are loath to publicly criticize the stem cell agency because it holds the strings to the purse that finances their careers.

California scientists, however, should be asking themselves a bottom-line question. Do they want to see the stem cell agency continue for another 10 to 20 years? Under the best of circumstances, that may be unlikely given the other pressing needs that the state faces. But if CIRM directors do not forthrightly address the recommendations of the IOM panel, the fate of the stem cell agency is exceedingly uncertain.

Patient Advocate Says IOM Recommendations Would 'Destroy' California Stem Cell Agency

California's “beloved,” $3 billion stem cell research program should not be altered despite recommendations from the most prestigious scientific organization of its kind. So says longtime patient advocate Don Reed of Fremont, Ca.

Reed says the recommendations by the Institute of Medicine (IOM) are a “threat” that would “destroy” an agency that “is like nothing else on earth.” Reed is urging other patient advocates to turn out at next week's critical meeting of the stem cell agency's board and lobby against alterations in how it does business.

Reed and CIRM's Amy Adams
World Stem Cell Summit photo

Reed is a fixture in stem cell circles nationally and in California and has been a regular at the stem cell agency's public meetings since 2004. He is also vice president of Americans for Cures, a private stem cell lobbying group created by Robert Klein when he was chairman of the stem cell agency,  formally known as the California Institute for Regenerative Medicine(CIRM).

Reed has written twice about the IOM report on his blog with duplicate publication on the Huffington Post. Yesterday, he said IOM “defies” the voters' will when they created the stem cell agency in 2004. On Dec. 19, he said the $700,000, 17-month study was “staggeringly misguided.” He wrote,

“If its recommendations were enacted, they would silence stem cell patient advocate involvement, eliminate public debate on funding proposals, and delegate the real decisions to secret proceedings by an out-of-state-controlled board.”

Reed described the stem cell agency as “fantastic” and wrote,

“So why mess with it, in such a brutal and insulting manner?”

This writer has known Reed since the early days of the stem cell agency and respects him. But in this case he has many of his facts wrong. To mention just a few key points: Patient advocates would not be silenced; their role would be changed. Public comment would not be eliminated. Scientists could still appeal negative decisions by reviewers to the full board if they so choose, although the “extraordinary petition” process would be eliminated. The voters' will would not be defied; they provided for a mechanism for making changes in the stem cell program.

While Bob Klein has not been heard from publicly on the IOM report, some of Reed's comments reflect Klein's past positions against altering the agency. Klein, an attorney and real estate investment banker, might well be considered the father of the agency. He directed the writing of the 10,000-word measure, Prop. 71, that created the program and wrote much of ballot initiative himself. The initiative contained a detailed description of the qualifications for the chairman, which fit only one person in California. It was no surprise when he won the post.

In years past, Klein has been extraordinarily protective of the ballot measure, at one point boxing in the board on earlier proposals for changes that he disliked and that the IOM report now echoes.

In 2010, he was the prime advocate for commissioning the IOM report which he expected to serve as the basis for continued funding of the agency. It will run out of cash for new grants in 2017.

To keep the money rolling in, Klein said the IOM report would constitute a “gold standard” that would generate increased enthusiasm for the research.

According to the transcript of the Aug.18, 2010, governing board meeting, Klein declared,

“(We will) never convince the people that are adamant against us. But for the public and for the constituent groups that are reasoned and prepared to look at evidence, this is a very important validation that they can look to to separate out what is a false claim from real performance.”

Also writing yesterday about the IOM study was Bradley Fikes of the San Diego U-T, the dominant daily newspaper in that area.

He summarized Reed's latest item as well as this on the California Stem Cell Report yesterday. Fikes plans to file his own story within the next few days.

Feel free to file your own comments by clicking on the word “comment” below or with the stem cell agency at info@cirm.ca.gov. Anonymous comments are permitted on this blog.