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."