Appeals at the California Stem Cell Agency: Worthwhile or Worthless?

Jon Shestack, a patient advocate member of the governing board of the California stem cell agency, weighed in today on the virtues of the grant application appeal process at the $3 billion research enterprise.

His remarks came in a “comment” filed on the Duchenne item that appeared yesterday on this site. (His full comment can be found at the end of that item.)

Shestack said that the handling of the $6 million CIRM grant involving Duchenne research is “a casebook study on why the special(extraordinary) petition is worthwhile. There was indeed new and relevant information that only became available after grant review. Scientific staff and leadership flagged it.”

The utility of the petitions is one of the reasons that we ran the story about Duchenne and the team at UCLA. The extraordinary petition process is currently under fire by both the Institute of Medicine and the stem cell agency itself, which has appointed a task force to come up with changes. But, while the petition process is certainly less than perfect, so is the peer review/grant review process.

The Duchenne application is not the only “case study.” An application by Karen Aboody of the City of Hope is often cited as another case. There are undoubtedly others.

The petition process was adopted several years ago by the board as a tool to manage willy-nilly appearances of scientists before the CIRM governing board whose applications were rejected by reviewers. Now the Institute of Medicine has recommended the petitions be abandoned, saying they undermine the integrity of grant review process. The IOM cited a major controversy in Texas involving its cancer research agency as an example of how grant reviews or the lack of them can go bad – not to mention conflict of interest problems there. CIRM has already started to look for better solutions regarding appeals. Many of its directors are troubled by emotional presentations from patients in connection with petitions and the lack of adequate information to make informed decisions on the spot about the contested matters.

Whether appeals can be put in a tidy, scientific box is debatable. Researchers have the right, under state law, to address the board on any issue whatsoever. And at least some of them will continue to do so -- regardless of any appeals changes --  when millions of dollars and their careers are at stake.

Opinions and decisions of CIRM reviewers are not holy writ. They can and do make mistakes, as we all do. In making changes in the appeals process, the goal of the agency should be to devise a public and transparent process rather than enshroud it in more secrecy. CIRM also should find a way to do a much better job of communicating to applicants the availability of appeals and precisely how to appeal when it becomes necessary.   

LA Times: On the California Stem Cell Agency and Wasting $700,000

The headline on the Los Angeles Times web site this afternoon read,

"Is California's stem cell program preparing to waste $700,000?"

The question was raised by Pulitzer Prize-winning columnist Michael Hiltzik, whowas commenting on the presentation today by the prestigious Institute of Medicine's (IOM) on its sweeping recommendations for changes at the state stem cell agency. 

Hiltzik wrote, 

"If you're betting that the California stem cell agency will spurn key recommendations of a blue-ribbon review panel that criticized its leadership and management structures, you might want to double that bet. Several board members showed overt hostility to the panel's recommendations during a public meeting today."

Harold Shapiro, chairman of the IOM panel and former president of Princeton University, delivered the briefing. The group's study took 17 months and cost the stem cell agency $700,000.

Hiltzik's piece summarized the IOM proposals, which echoed many criticisms that have been aired for years in California.  Hiltzik wrote, 

"CIRM Chairman Jonathan Thomas glided over those issues when he introduced Shapiro. Thomas observed that the Institute of Medicine report included many statements "validating CIRM, its process, what it was able to achieve," which is a bit like launching the investigation of a plane crash by focusing on all the planes that land safely every day. Thomas did mention that the Institute of Medicine had made numerous recommendation about how to "take something which is already a great experience and improve it even further." 

"Shapiro got only a few minutes into his presentation before board members started interrupting him with objections to the Institute of Medicine's recommendation for a majority of independent members."

Hiltzik concluded, 

"Thomas promised to stage a public workshop on the Institute of Medicine report soon and to subject them to 'lengthy discussion.' 

"Does that sound as if the board will be taking seriously the advice that it change the way it does business? Stay tuned, but don't hold your breath."

Winners From Today's Awards by the California Stem Cell Agency

The 12 winners in the latest round of grants from the California stem cell agency all come from institutions linked to directors on the agency's governing board. Board members with conflicts of interest are not allowed to vote on the grants or participate in the debate. Since the inception of the agency, more than 90 percent of its awards have gone to institutions linked to the directors. Here is a link to the CIRM press release on today's meeting.

Here is the list of researchers who won awards today.

New Faculty Physician Scientist Translational Research Awards

RN3-06530	Robert Baloh	Cedars-Sinai Medical Center	$3,031,737.00
RN3-06378	Reza Ardehali	University of California, Los Angeles	$2,930,388.00
RN3-06504	Jason Pomerantz	University of California, San Francisco	$3,084,000.00
RN3-06396	Mana Parast	University of California, San Diego	$3,013,252.00
RN3-06425	Tracy Grikscheit	Children's Hospital of Los Angeles	$3,408,000.00
RN3-06532	Tippi MacKenzie	University of California, San Francisco	$2,661,742.00
RN3-06479	Ann Capela Zovein	University of California, San Francisco	$3,084,000.00
RN3-06529	Alan Cheng	Stanford University	$3,091,595.00
RN3-06455	Ali Nsair	University of California, Los Angeles	$3,004,315.00
RN3-06460	Emanual Maverakis	University of California, Davis	$2,964,000.00
RN3-06510	Michelle Monje	Stanford University	$2,800,536.00
RN3-06525	Ophir Klein	University of California, San Francisco	$3,084,000.00
Total			$36,157,565.00

ViaCyte Wins Another $3 Million from California Stem Cell Agency

The California stem cell agency, which has awarded ViaCyte, Inc., $36 million, today pumped another $3 million in the firm following the collapse of an alliance between the San Diego firm and GlaxoSmithKline.

The now failed ViaCyte-Glaxo-CIRM arrangement was ballyhooed by the CIRM in October because it would have been the first deal involving Big Pharma and the stem cell agency. The resources of Big Pharma are needed to pursue the expensive path of turning stem cell research into cures.

Meeting in Los Angeles, the CIRM governing board approved the additional funds on a 13-0 vote with two abstentions.  The action came following a closed door session to discuss how the funds would be spent. No details were provided publicly on that matter.

ViaCyte has also told Biocentury that it is pursuing even more funding after the alliance with Glaxo broke down. CIRM President Alan Trounson said ViaCyte is likely to receive another $3 million from the Juvenile Diabetes Research Foundation. Trounson also said that other sources are being examined as well. 

Patricia Olson, executive director of CIRM, scientific activities said the agency's advisors continue to have faith in ViaCyte's effort to develop a treatment for diabetes. The company plans to start a clinical trial on its product in 2014.

The ViaCyte-Glaxo-CIRM deal was cause for celebration last fall. Alan Trounson, CIRM's president, said the deal would “resound” globally. He told directors,

 “This is verification of our program. To have (the head of Glaxo regenerative medicine program) join us through a partnership arrangement with GSK means that a project that we've shepherded from the basic science through to the preclinical work and is heading to the clinic we're now going to do in partnership with a very major organization.”

California Stem Cell Directors Adjourn Meeting

Today's meeting of the governing  board of the California stem cell agency has adjourned. We will have an item coming up shortly on approval of $3 million for ViaCyte, Inc., of San Diego.

Constitutional Questions Raised on Sweeping Changes at the California Stem Cell Agency

The outside counsel to the governing board of the California stem cell agency is preparing an opinion on whether some of the major changes recommended by the blue-ribbon Institute of Medicine(IOM) study might require a vote of the people.

More than three years ago, the same issue was raised  and used by the agency to resist unwanted changes.

Kevin McCormack, agency spokesman, said today that James Harrison of Remcho Johansen & Purcell of San Leandro will perform the analysis. Harrison has been counsel to the CIRM board since its inception. He also wrote part of Proposition 71, which created the stem cell agency in 2004.

Harrison's analysis was disclosed after CIRM Director Sherry Lansing, who is also chairwoman of the University of California Board of Regents, said this morning that the board's "hands are tied" concerning some of the IOM proposals because they could require a vote of the people. Other members of the board bristled at the IOM recommendations.

In 2009, Harrison tackled a similar task in connection with related, proposed structural changes at the $3 billion stem cell research effort. In reaction to proposals by the Little Hoover Commission, the state's good government agency, Harrison said,

“The Little Hoover Commission’s proposals would effect drastic and disruptive changes to CIRM’s governance and operating systems. Such changes run counter to the voters’ intent, and do not further Proposition 71’s purposes.”

The California Stem Cell Report wrote at the time, 

"The 10-page legal memo hung most of its arguments on a provision in Prop. 71 that states that it can only be amended by the legislature if the changes 'enhance the ability of the institute to further the purposes of the grant and loan programs.'
"Harrison's memo said the Hoover proposals (in question) could only be enacted through another ballot measure...."

The Little Hoover proposals dealt with the structure of the board and the conflicting responsibilities of the president and the chairman. The IOM has recommended major changes in both areas and approvingly cited the Hoover study .

Harrison's analysis will also delineate which IOM recommendations can be implemented by board action and which will require legislative approval.

The IOM report, which cost the stem cell agency $700,000, recommended a host of changes that critics for years have said are needed. But the 17-month study also went beyond what the critics had proposed. The IOM said that the 29-member governing board should be stripped of power to approve individual grants. Instead, the board would be limited to voting for or against a slate of applications.

The IOM also proposed far-reaching changes to remove conflict of interest problems, clean up a troubling dual-executive arrangement and fundamentally change the nature of the governing board. The recommendations would 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.

CIRM's governing board and its first chairman, Robert Klein, an attorney who directed the writing of the stem cell initiative and wrote parts of it, have mightily resisted related proposals. In 2009, Klein even warned of lawsuits if legislative action were initiated for reforms (see here and here). 

In an editorial today, The Sacramento Bee said changes are long overdue at the agency. The Bee said CIRM has "been consumed by a siege mentality that has prevented any real introspection.”  In another editorial earlier this week, the San Francisco Chronicle said that prompt and major changes are needed at the agency.

Many of the more significant recommendations clearly require either a rare, super, supermajority vote of the legislature (70 percent) and the signature of the governor or another ballot initiative, which is very unlikely. Achieving the 70 percent vote is exceedingly difficult except on the most noncontroversial matters before the legislature. The requirement permits only 13 members of the 40-member Senate to block any CIRM legislation, giving minority viewpoints extraordinary power over the content of any CIRM legislation.

(See here for a list of IOM recommendations that would likely require legislative action.)

CIRM Directors Approve $36.2 Million in Stem Cell Grants

Directors of the California stem cell agency today approved $36.2 million for 12 physician-scientists, turning down four appeals from scientists whose applications were rejected by reviewers.

Names of the winners were not immediately disclosed, although the agency will publish their names later today. The vote on the individual grants also was not announced.

Here are links to items dealing with the appeals and the grant round. See here, here and here.

CIRM Directors Discussing $36 Million in Grants

Directors of the California stem cell agency are currently discussing possible awards in a more than $36 million round of grants. One appeal seems to have failed when one director backed away from an expression of interest. The appeal involved research on a stem cell-based pacemaker by Eugenio Cingolani of Cedars Sinai in Los Angeles.

(An earlier version of this item said the amount was more than $32 million.)

A Singular Scientific Story: Duchenne's Disease, a Family and the California Stem Cell Agency

Unusual and personal conditions, including a tie to the $3 billion California stem cell agency, surround a promising scientific development reported today by a husband and wife research team at UCLA. 

Their research involves Duchenne muscular dystrophy (DMD), an inherited disease that afflicts about one in 3,600 boys and results in muscle degeneration and, eventually, death.

Carrie Miceli
UCLA photo

The researchers, Stan Nelson and Carrie Miceli, said they have discovered a promising FDA-approved drug that could advance the fight against the affliction.

Miceli and Nelson have an 11-year-old son, Dylan, with the disease. They have been studying the affliction for some time, but their most recent and ambitious research plan was rejected earlier this year by stem cell agency grant reviewers, a process that normally kills an application. Undaunted, Miceli and Nelson appealed to the full stem cell agency board last July. Backed by an emotional presentation involving patient advocates, they won approval of a $6 million grant.

Adding to all this, their appeal used a process known as an “extraordinary petition,” which the Institute of Medicine (IOM) last week said should be abandoned because it undermines the integrity of the CIRM grant review process.

Stan Nelson
UCLA photo

Even prior to the IOM recommendation, the CIRM board was moving to restrict its free-wheeling appeals procedures.

As for the $6 million CIRM grant, it will carry the important burden of advancing the findings that were published in the journal Science Translational Medicine. However, the money was not used in the study reported today.

The research showed that dantrolene, the FDA-approved drug, “provides a powerful boost to the (Duchenne) therapy currently being tested in clinical trials,” according to a UCLA press release.

The news release said,

“(The researchers) hope this one-two punch used in combination will overcome the genetic mutations that cause DMD, restore a missing protein needed for proper muscle function and allow those affected by the disease to lead relatively normal lives.”

“Their youngest son, Dylan, 11, was diagnosed with DMD in 2004. While he’s still ambulatory – many DMD patients require the use of wheelchairs by about age 10 – Dylan can no longer run or climb stairs and he can’t shoot a basketball over his head like other boys his age.  Despite these challenges, Miceli said Dylan remains a happy, funny and engaged boy, full of life and passion.

“'We entered into this field because of the diagnosis of our son, but we hope our research can help many others,' she said. 'There are drugs that can help manage the symptoms of the disease, but nothing that changes its course dramatically. We’re trying to correct the defect that causes DMD with highly personalized genetic medicine.'” 

UCLA said the grant from CIRM will be used for “longer term studies of their drug combination therapy in mouse models to ensure it can restore dystrophin levels to normal or near normal levels. They also will explore whether DMD patients with other mutations can benefit from the combination therapy.”

Asked for comment, Kevin McCormack, a spokesman for the stem cell agency, said today's findings "are certainly very encouraging." He continued,

"Clearly there is still a long way to go before we know if this approach will work in people but we're delighted that funding from the stem cell agency is helping  the researchers move their work forward....This is what voters set out to do when they approved Proposition 71 to create the stem cell agency."

Some California Stem Cell Board Members Bristle at IOM Recommendations

Some directors of the $3 billion California stem cell agency today sharply challenged recommendations by the Institute of Medicine(IOM) concerning conflicts of interest and the role of patient advocates on the governing board.

Much  of the criticism came from the 10 patient advocate members on the board, whose roles would be significantly altered  under the IOM recommendations. Jeff Sheehy, a patient advocate for HIV/AIDs and vice chairman of the agency's grant review group, said he saw no evidence in the IOM report for its recommendations regarding patient advocates. He said,

 "If you had some here, I would be more comfortable." 

He continued,

"We are not all powerful. We are a minority on the (29-member) board." 

Jonathan Shestack, another patient/adovcate director, said the IOM's conclusions on "conflicts of interest could not possibly be more incorrect than they are." He said,

"Advocates are here to advocate."

Harold Shapiro, chairman of the IOM study, said, "We are not against patient advocates." He said that the IOM supports advocates and that its recommendations could increase the role of patient advocates, albeit in a different manner.

Shapiro added that conflicts of interest do not necessary bar participation by board members. He said, however, they must be disclosed and managed.

Director Robert Price of UC Berkeley said,

 "We have gone to great lengths to manage conflicts of interest."

The IOM recommended that all board members be removed from the grant review process, which would be turned over to the CIRM president. The board would only vote on a slate of applications, not individual grants. More disclosure would be required of personal conflicts of interest, including health matters, that the board said research has shown can create bias.

 The IOM report 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(the CIRM governing board), introduce potential bias into the board’s decision making, and threaten to undermine confidence in the board.”

More than 90 percent of the $1.7 billion that the CIRM board has awarded has gone to institutions that are represented on the CIRM governing board.

J.T. Thomas, chairman of the CIRM board, said that the agency takes the recommendations "very seriously" and that they would discussed further at a board workshop in early January. The workshop is scheduled to be public but the date and location has not been announced. Thomas said the recommendations will receive "lengthy discussion" thereafter and review by appropriate subcommittees of directors.

No one from the public commented during the roughly 90 minute discussion.  Eighteen out of 29 board members were present at the beginning of today's meeting.

IOM Report: Many Major Changes at Stem Cell Agency Require Legislation

As the Institute of Medicine began its presentation today to the governing board of the $3 billion California stem cell agency, one of its key directors, Sherry Lansing, pointed out that some of the IOM recommendations require legislative action and perhaps a vote of the people.

Her essential point was that the agency is hamstrung by the very measure that created it in 2004. She did not elaborate on her comment, but here is a look at some of matters she was talking about. (Lansing is chairwoman of the UC board of regents and former CEO of a Hollywood film studio.)

The ballot measure locked in management minutia and more, and then slapped on tight restrictions that make it nearly politically impossible to alter even such matters as who is in charge of production of the annual report. (By order of law, the chairman, in case you are wondering.)

And if the 29-member governing board -- so sized and specified to every nit and nat by the ballot measure -- wants to make the sweeping changes recommended by the IOM, agency directors face a formidable task in California's Capitol.

Many of the most important recommendations for the California stem cell agency require a vote of the California legislature and signature of the governor. The IOM's choice of words – that these proposals “may” need legislation – is conservative. There is little doubt that legislative action would be needed to fully implement the recommendations below.

The vote needed is no simple majority. It is a rare, super, super-majority (70 percent) of each house. The requirement was also written into state law by Proposition 71, the 10,000-word ballot initiative that created the stem cell agency. The 70 percent requirement gives extraordinary power to minority viewpoints that must be dealt with to win passage of legislation. In the state Senate, for example, it would take only  13 senators to block a bill.  

With that background, here are direct quotes from the IOM report on its legislative recommendations.

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.

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 terms of board members should be staggered to balance fresh perspectives with continuity.

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.

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.

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 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.

The committee recommends several changes pertaining to the development and approval of RFAs, composition of the Grants Working Group, reordering of rankings by CIRM staff, notification of applicants, and process for making final decisions.

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.

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.  

IOM Presentation Begins

The first order of business at today's meeting is the presentation by the Institute of Medicine of its $700,000 study of the $3 billion California stem cell agency. Harold Shapiro, chairman of the IOM study, and Terry Magnuson, vice chairman, will conduct the briefing.

Stem Cell Board Meeting Begins

Today's meeting of the governing board of the California stem cell agency has just begun. Roll is being called. The pledge of allegiance is being recited.

Covering the California Stem Cell Agency from Panama

For those of you interested in the unlovely details of how we cover the  California stem cell agency, here is a quick look at the process for today's meeting.

We are anchored in a sailboat in Panama Bay off the City of Panama. We will attempt to log into a phone broadcast of the agency's governing board meeting in Los Angeles using the instructions provided on the meeting agenda. That will happen, we hope, using Skype, which can sometimes be dicey here. Our Internet connection is a via a USB modem to a Claro 3.5G wireless phone service. It is a prepaid account for "unlimited" use at $15 a month. We also have a cellular phone with prepaid service, as a possible backup, with a different provider. But that could prove to be very expensive for an eight-hour meeting.

On past board meetings, we used CIRM's Internet audiocast, which had its problems from time to time. CIRM appears to have dropped that service.

Sacramento Bee and IOM: Restructuring Needed at California Stem Cell Agency

The Sacramento Bee today praised the Institute of Medicine (IOM) recommendations for wide-ranging changes at the $3 billion California stem cell agency.

The newspaper's editorial and an earlier one in the San Francisco Chronicle come as the IOM formally presents its findings this morning to CIRM directors, some of whom would likely lose their seats if the recommendations are implemented.

The Bee said that for years “numerous outside critics” have recommended similar changes at the state agency to avoid conflicts of interest and possible misuse of public funds. The Bee wrote,

“Instead of listening, leaders of this institute(CIRM) – a poster child of how ballot initiatives can be manipulated to create quasi-public institutions with little public oversight – have been consumed by a siege mentality that has prevented any real introspection.”

The Bee noted that about 90 percent of the $1.7 billion handed out by the eight-year-old agency has gone to institutions connected to members of the 29-member governing board. One of the IOM recommendations would bar the board from voting on individual grant applications. Instead, the applications would be voted on as a block.

The Bee continued,

“It is to CIRM's credit that it solicited the Institute of Medicine report last year. Although some taxpayers may blanch at the report's $700,000 price tag, it will be worth the cost if it leads to a restructuring of how CIRM operates. 

“Of course, if it fails in that task, it will only affirm the view of many voters that they should never again endorse a California research initiative, especially one like Prop. 71 that lacks proper controls and accountability over taxpayer dollars.”

Coming Up: Live Coverage of IOM Presentation to Directors of the California Stem Cell Agency

The California Stem Cell Report will begin its live coverage today of the meeting of the governing board of the California stem cell agency at 9 a.m. PST (Noon EST). On today's agenda is the official presentation of the IOM's sweeping recommendations to the agency's directors. Stories will be filed as warranted.

For information on how to listen to the meeting live or find one of the teleconference locations in California, see this item.

Neil Littman: New Business Development Officer at the California Stem Cell Agency

The California stem cell agency this week mentioned the hiring of a business development officer as part of its plan to engage industry more robustly but did not identify him.

Neil Littman
Linked In photo

The California Stem Cell Report queried the agency about the new hire. Kevin McCormack, the agency spokesman, identified him as Neil Littman, who most recently worked as a senior associate in the merchant banking group at Burrill & Co. in San Francisco.

Littman's responsibilities will include “facilitating opportunities for outside investment in stem cell research in California for both CIRM-funded and non CIRM-funded programs by biopharmaceutical strategic partners, equity investors and disease foundations.”

McCormack said that Littman's “strategic advisory experience includes buy-side and sell-side M&A, as well as in-licensing and out-licensing of both development stage and commercial products.”

Littman also worked at Thomas Weisel Partners and at Deutsche Bank Securities. He received a M.S. in biotechnology with a concentration in biotechnology enterprise from The Johns Hopkins University, and a B.A. in molecular, cellular and development biology from the University of Colorado Boulder in 2002. 

Littman's salary at CIRM is $160,000 annually.

StemCells, Inc., and California Stem Cell Agency Remain Stalled over $40 Million

The California stem cell agency and StemCells, Inc., are still stalled in negotiations over how the firm will become eligible for $40 million from the state research effort – three months after the agency's governing board approved the awards.

The key issue is whether the agency is satisfied that the Newark, Ca., firm can provide $40 million in matching funds that it promised under the terms of two $20 million awards approved in late July and early September. The September award was approved on a 7-5 vote by agency directors after it was rejected twice by CIRM reviewers.

In response to a query by the California Stem Cell Report, Kevin McCormack, an agency spokesman, yesterday said the company and CIRM have not reached agreement.

CIRM directors okayed the September award in an appeals process that used a mechanism called “extraordinary petitions.” Last week, a blue-ribbon, Institute of Medicine study of the agency said the petitions should be abolished because they damage the integrity of the grant review process.

The September approval was the first time that agency directors approved an application that was rejected twice by reviewers. The action followed two appearances by the former chairman of the agency, Robert Klein, on behalf of StemCells, Inc. It was his first such appearance on behalf of an applicant.

The StemCells, Inc., award also triggered a column in the Los Angeles Times by Pulitzer Prize-winning columnst Michael Hiltzik. He wrote that the process was “redolent of cronyism” and said a “charmed relationship” existed among StemCells, Inc., its “powerful friends” and the stem cell agency.

StemCells, Inc., stock price reached a 52-week high on Sept. 4 of $2.67, well up from its 52-week low of 59 cents June 4. The stock was trading at $1.78 at the time of this writing.   

IOM-Stem Cell Agency Coverage Planned for Tomorrow

The California Stem Cell Report tomorrow will provide complete, live coverage of the Institute of Medicine (IOM) presentation to the directors of the $3 billion California stem cell agency. The IOM last week recommended sweeping changes at the agency, but this is the first chance for the agency governing board to hear directly from the panel.

Harold Shapiro, chairman of the IOM study committee and former president of Princeton University, and Terry Magnuson, vice chairman of the panel and vice dean of research at the University of North Carolina, will perform the briefing for the 29 members of the CIRM governing board.

The meeting is scheduled to begin in Los Angeles at 9 a.m. PST. Our best guess is that the IOM presentation will come up shortly after the meeting starts.

Those who would like to listen live to the meeting can dial 866-254-5937 and use the code 274426 to hear the meeting on a one-way connection. The stem cell agency is no longer providing an Internet audiocast.

In California, teleconference locations that permit comment and participation in the meeting are available in San Francisco, Pleasanton and La Jolla. A previous location in Oakland is no longer available. Persons interested in those locations should check with CIRM for more details on the specific locations than is provided on the agenda.

The agency has also published its Power Point presentations dealing with the initiation of a $40 million basic biology round, the proposed awards of more than $36 million for translational research and the agency's industry engagement plan. Four rejected applicants have appealed in translational research round, which was budgeted for $80 million.

You can read more about the IOM report here, here, here and here.

Four Researchers File Appeals with Stem Cell Board for Millions of Dollars

Two more scientists are seeking to overturn rejection by reviewers of their applications for millions of dollars from the California stem cell agency, bringing to four the number of appeals in the award round to be considered Wednesday by agency directors.

The latest two are Sanaz Memarzadeh of UCLA and Eugenio Cingolani of Cedars Sinai in Los Angeles. Memarzadeh is seeking $3.1 million for research into the causes of endometriosis. Cingolani is seeking $2.8 million to research the possibility of a stem-cell based heart pacemaker.

Both have filed “extraordinary petitions” with CIRM, an appeals process that the Institute of Medicine last week said should be jettisoned by the agency. The IOM said the petitions undercut the integrity of the grant review process. At the same time, directors of the agency are mulling changes in the appeals process, which has seen a record number of appeals, including emotional presentations by patients at board meetings. Both petitions were written prior to the release of the IOM report.

In her petition, Memarzadeh said,

Sanaz Memorzadeh
UCLA photo

“Endometriosis is the third most common non-lethal chronic disease in California affecting 1 in 10 reproductive age women and costing the state $25 billion annually.”

Endometriosis occurs when cells from the uterus grow in other areas of the body often causing debilitating pain and sometimes pelvic cysts, according to the NIH, and the best chance for a cure is removal of reproductive organs.

Memarzadeh said the cause is unknown as are the best ways to treat the affliction. She wrote,

“To our knowledge CIRM has not funded any work related to women’s gynecologic diseases. Funding work related to endometriosis through this proposal is an opportunity for CIRM to fill a critical gap and make a major impact in this understudied field of research.”

Eugenio Cingolani
Cedars Sinai photo

Cingolani also said his research is not represented in the CIRM portfolio. He said,

“While CIRM has laudably invested in ischemic heart disease studies, no grants have been awarded in the area of heart rhythm disorders. This is a huge area of public health need. The current application has the potential to fill an important gap in the current CIRM translational research portfolio, expanding the focus to treat heart rhythm disorders.”

In this round, which was budgeted at $80 million, 12 grants were approved by reviewers. Fifteen were rejected. The amount required for the 12 grants is $36.2 million.

The stem cell agency did not release the scores of the grants that were rejected. They are likely to be disclosed at the Wednesday meeting.

IOM Report: Chronicle Says Prompt and Major Changes Needed at Stem Cell Agency

The San Francisco Chronicle today said the $3 billion California stem cell agency needs to make major changes “to avoid conflicts of interest and retain its credibility with the public, and it needs to do so sooner rather than later.”

In an editorial that came in response to the sweeping recommendations of the Institute of Medicine last week, the Chronicle declared,

“The California Institute for Regenerative Medicine (CIRM), the stem cell funding agency that state voters approved in 2004, has been an 'innovative initiative' that's strengthened California's biotechnology industry and furthered the cause of basic stem cell research, according to a new independent review by the Institute of Medicine (IOM). But the agency needs to make some major structural changes in order to avoid conflicts of interest and retain its credibility with the public, and it needs to do so sooner rather than later.”

The editorial continued,

“The institute also needs to respond to the criticisms in the report, and to do so as quickly as possible. In particular, the institute needs to reform its management if it's to continue its mission after state funding runs out, as it appears the institute's chairman would like to do. Its governing board is too involved in day-to-day management. Nearly all the 29 members of that same board are on the payroll of institutions that have won grants - a serious conflict of interest.”

The Chronicle editorial was the first that we have seen on the subject, but additional comments from individuals have come the way of the California Stem Cell Report.

In an email, Tom Hall, a retired history professor in Berkeley, said,

“At the risk of being too cynical, it seems to me that those who expect the agency to implement the proposals are being more than a bit naïve. The proposals amount to asking people to commit suicide. Those presently involved have too much self-interest at stake to voluntarily drop out. Some kind of pressure will have to be applied.”

Hall referred to IOM recommendations that the 29-member CIRM governing board be barred from voting on individual grant applications and its members be removed from the grant review process. The IOM also said that the majority on the board should consist of “independent” members, which would likely mean that some current board members would lose their seats.

Another email from a person with close knowledge of the stem cell agency, but who must remain anonymous, said,

“I worry that CIRM (governing board) will once again circle the wagons and construct elaborate excuses for inaction and preserving the status quo. It's really terrible because you could make incredible advances if only the energy and dollars were directed properly.”

The Sacramento Bee ran a related editorial yesterday that called for “putting the brakes” on "the initiative machine," which was the process used to create the stem cell agency in 2004. The Bee said that initiatives are “driven by special interests and buttressed by a business network of signature gatherers, legal services and campaign consulting.”

The stem cell initiative, Proposition 71, also has become a two-edged sword for the agency, locking in management minutia and making it nearly impossible to make needed changes, such as those recommended last week by the blue-ribbon Institute of Medicine panel.

Among other things, The Bee indicates that it would support “a sunset of 10 to 15 years for laws passed by voters – or automatically putting such laws back on the ballot for voters to reject or affirm.”

The Bee has yet to editorialize directly on the IOM report.

California Stem Cell Agency: Two Researchers Seek to Overturn Grant Review Rejection

Two University of California scientists whose applications for millions of dollars were turned down by reviewers at the California stem cell agency are asking its governing board this Wednesday to overturn the rejections.

They are Jonathan Lin of UC San Diego and Sophie Deng of UCLA, who are seeking $3.1 million and $3 million respectively.

They have filed appeals using a process known as extraordinary petitions, which a blue-ribbon report by the Institute of Medicine last week said should be abandoned. The study on the performance of the $3 billion agency said the petitions “undermine the credibility and independent work” of grant reviewers.  However, under state law stem cell researchers and the public have the right to address the CIRM board on any issue whatsoever.

In recommending abolition of the petitions, the IOM cited the flap in Texas concerning its $3 billion cancer research program. Reviewers there resigned en masse to protest what they considered abuse of the grant review process.

Lin and Deng's petitions were written prior to the release of the IOM report.  But they come as the agency is already examining ways to tighten up its free-wheeling appeal process, which this year has seen a record number of appeals, backed by emotional presentations from patients and lobbying by the former chairman of the agency, Bob Klein.

In the grant round to be considered Wednesday, reviewers have approved 12 applications out of 27 generated by the “New Faculty Physician Scientist Translational Research” RFA. The approved grants have scientific scores ranging from 87 to 65. Positive decisions by reviewers are almost never overturned by the CIRM board. The approved applications total $36.2 million, according to California Stem Cell Report calculations. The agency budgeted $80 million for the round. One application, the proposal that scored 65, was approved for what CIRM calls “programmatic” reasons, which have been defined as “issues beyond scientific merit, such as disease representation and societal impact.”

In her petition, Deng challenged the reviewers' remarks that her proposal was not worthy of funding because it is “not exceptionally novel.”

Sophie Deng
UCLA photo

She wrote,

“This comment reflects a misunderstanding of translational research. There is a huge gap between a novel discovery and delivering a new therapy to the clinic; translational research is about bridging this gap, not the novelty of the discovery. If the discovery is not translatable, it is meaningless for patient care....Our approach might not be the most novel, but it has the highest potential to bring a new therapy to the clinic.”

Deng also said that “multiple criticisms” in her review “reflected flawed understanding” of its clinical aspects.

Lin's petiton was briefer. He said an attempt to approve the application for programmatic reasons during the review failed because “CIRM was already funding AMD (age-related macular degeneration), and that significant progress was being made elsewhere in the world.”

Lin said,

Jonathan Lin
UCSD photo

“I contest these claims because CIRM has not funded AMD-related research in prior New Faculty Physician Scientist Translational Research RFAs. Furthermore, stem cell research to treat AMD remains in basic science, preclinical research, and clinical safety phases in California. Significant research and clinical studies are still ahead before stem cells can be approved for therapeutic use in patients with AMD.”

CIRM did not disclose the scores of either Lin or Deng. Only the scores of approved applications were listed for this meeting. In some cases in the past, scores of some rejected grants have been listed on the CIRM web site. The agency did not disclose the names of the other applicants or their institutions. 

$40 Million High-Risk Stem Cell Research; IOM and CIRM on Engaging Biotech Biz

Directors of the California stem cell agency this Wednesday will be asked to approve initiation of a $40 million, high-risk research program aimed at filling “key gaps” in knowledge about human stem cell behavior.

The concept plan for the round – called Basic Biology V – will come up for approval at the governing board meeting in Los Angeles.  Pre-applications are expected to be due in March.

The staff proposal calls for as many as 30 awards, but did not specify a limit on the total dollars for each award. The competition is open to both business and academics and non-profit organizations.

The proposal said that the round is targeting “high-risk, exploratory pursuits.” The goal is to fill “key gaps in our understanding of fundamental human stem cell behaviors that hinder the pace of discovery, and ultimately prevent the potential of this research from being fully realized.”

Additionally up for consideration at this week's meeting is a “blueprint” for “engaging industry and supporting commercialization” of CIRM research. A blue-ribbon study by the Institute of Medicine last week also recommended that CIRM engage industry more warmly. However, there were striking differences between what the IOM recommended and what CIRM proposed. The CIRM plan was prepared prior to the release of the IOM report. 

The CIRM proposal laid out the following objectives that were prompted by an “external review” two years ago.

•  “Attract Follow-On Financing and Co-funding of CIRM Funded Research
•  “Support of Company Creation/Growth/Relocation
• “Early Engagement of Top Tier Biopharmaceutical Companies in Order to Access Critical Expertise
• “Assume a Leadership Role in Business Related Areas the are Critical for Supporting the Field”

The CIRM memo listed a number of initiatives that the agency has already started and said more are expected to come. They include the already enacted, new business-friendly award program, the recent hire of an unidentified business development officer, designation of industry “collaborators,” relocation support for high impact companies and participation with industry in developing “reimbursement pathways” that will benefit the regenerative medicine industry.

“Reimbursement” is the euphemistic term that industry prefers instead of saying “beefing up profits.”

Last week, the report by the Institute of Medicine, which cost CIRM $700,000,  noted that biotech firms have received only about 6 percent of the $1.7 billion handed out by CIRM, a figure not mentioned by the eight-year-old agency's industry engagement plan.

The IOM said that industry representation on the agency's critical, decision-making boards (the governing board and standards and grant reveiew groups) should be enhanced. Additionally, a new scientific advisory board with substantial industry presence should be created to replace existing advisory groups. All of which would be aimed at enhancing and leveraging industry “expertise and resources in product development, manufacturing, and regulatory approval in support of the ultimate goal of bringing therapies to patients,” according to the IOM.  

Stem Cell Agency Chairman Says IOM Report 'Quite Complimentary'

Jonathan Thomas
CIRM Photo

Jonathan Thomas, the Los Angeles bond financier who is chairman of the $3 billion California stem cell agency, has weighed in at more length on the sweeping recommendations from the Institute of Medicine for changes at the agency.

He wrote a piece for the agency's blog that said the 124-page report was “quite complimentary.” Thomas' article carried forward the theme of the stem cell agency's press release yesterday that said the IOM “praises the agency as a 'bold social innovation.'”

Thomas did acknowledge that the report “highlighted some areas and made some recommendations about where and how we might improve our performance.” 

Thomas concluded by saying the agency takes the report seriously and will, over the next few months, consider how best to respond.

Nearly needless to say, other observers of the agency differ with Thomas' characterization of the report as “quite complimentary.(See here and here.)

IOM Proposals for Overhaul at CIRM Win High Marks

The Institute of Medicine's recommendations for major changes at the California stem cell agency today received generally high marks from independent observers and critics.

Many of the proposals echoed suggestions from California's Little Hoover Commission, the state's good government agency. Asked for comment, Stuart Drown, the commission's executive director, said,

“The institute’s recommendations for much-needed changes to CIRM’s governance structure to provide greater efficiency, clarity and accountability reinforce the recommendations the Little Hoover Commission made in 2009."

He continued,

“Then and now, the Commission’s recommendations are aimed at improving CIRM’s ability to meet its goals for the good of all who can benefit from stem cell research, and to ensure that California taxpayers’ dollars are put to their most efficient use to that end.”

The California Stem Cell Report also asked the agency's first president, Zach Hall, for his thoughts. Here is the full text of what Hall, who was one of the peer reviewers on the IOM study, had to say,

“The IOM Committee and its staff have done an impressive job.  The report recognizes the scientific value and achievements of the CIRM and, at the same time, makes cogent recommendations that, if taken seriously, will further improve the quality and the public credibility of the Institute. The committee and staff deserve the thanks of the scientific community and all California citizens for their careful and thoughtful work.” 

John M. Simpson, stem cell project director for Consumer Watchdog of Santa Monica, Ca., said,

“It's long past time to make the changes the report calls for, but given the spin the agency put on its response -- saying the report praises the 'agency as a bold innovation' -- shows it's business as usual. This sort of behavior will only ensure that CIRM doesn't get another round of public funding,” 

Marcy Darnovsky, associate executive director of the Center for Genetics and Society of Berkeley, Ca., welcomed the recommendations. But she said,

“Given the agency’s shortcomings and the state’s budgetary problems, it would be wrong to ask Californians to give it more public money. If the agency acquires new funds from industry sources or venture firms, it must recognize that it has ongoing obligations to the people of California.” 

She continued,

 “CIRM has not responded in a meaningful way to many previous public interest suggestions or to independent reviews, including the one in 2009 by the state’s Little Hoover Commission. We hope the agency will not continue that pattern.” 

The California Stem Cell Report also queried most of the 10 patient advocates on the agency's governing board for comment. Their roles could be altered in a major way by the IOM recommendations. None of the advocates have yet responded.

(The full text or nearly full text of all the above comments is available here.)  

Text of Comments Reacting to IOM Report on California Stem Cell Agency

Here is the full text or the essential elements of comments sought by the California Stem Cell Report on the Institute of Medicine report that recommended sweeping changes at the California stem cell agency. Consumer Watchdog and the Center for Genetics and Society put their comments in the form of news releases, which contained redundant material.

From Stuart Drown, executive director of California's Little Hoover Commission:

“CIRM initiated the Institute of Medicine review, which is to its credit.  The Institute of Medicine took a scrupulous and rigorous approach to its review of the California Institute of Regenerative Medicine and in its report, notes CIRM’s many achievements and accomplishments.

“The Institute’s recommendations for much-needed changes to CIRM’s governance structure to provide greater efficiency, clarity and accountability reinforce the recommendations the Little Hoover Commission made in 2009. The institute graciously acknowledged the commission’s work, which clearly is as relevant now as it was in 2009.

“Then and now, the Commission’s recommendations are aimed at improving CIRM’s ability to meet its goals for the good of all who can benefit from stem cell research, and to ensure that California taxpayers’ dollars are put to their most efficient use to that end.”

From John M. Simpson, stem cell project director at Consumer Watchdog of Santa Monica, Ca.(full press release here):

“Consumer Watchdog Thursday welcomed a report from the prestigious Institute of Medicine (IOM) calling for sweeping reforms in governance at California’s stem cell agency and an end to the board’s built-in conflicts of interest. 

“The report said that 'far too many board members represent organizations' that receive funding or benefit from the stem cell agency. The IOM said that the board’s oversight function should be separated from the day-to-day management of the California Institute for Regenerative Medicine (CIRM). 

“'The IOM's critical report echoes what every independent evaluator has said in the past,' said John M. Simpson, Consumer Watchdog’s Stem Cell Project director. 'As we have repeated from the beginning, CIRM suffers from built-in conflicts of interest and needs to separate the board's oversight function from day-to-day management.'

“'It's long past time to make the changes the report calls for, but given the spin the agency put on its response -- saying the report praises the 'agency as a bold innovation' -- shows it's business as usual. This sort of behavior will only ensure that CIRM doesn't get another round of public funding,' Simpson said.”

From Marcy Darnovsky, associate executive director of the Center for Genetics and Society in Berkeley, Ca.(full press release here):

“The Center for Genetics and Society, a nonprofit policy research and advocacy organization, welcomed the report on the California stem cell agency released today by the Institute of Medicine and called for stronger protections for  the interests of Californians as the agency continues its disbursement of public funds.

“CIRM is nearing the end of the billions of dollars of public funding allocated to it in 2004. The agency is currently considering how to extend its operations after the money runs out. CGS Associate Executive Director Marcy Darnovskysaid, “Given the agency’s shortcomings and the state’s budgetary problems, it would be wrong to ask Californians to give it more public money. If the agency acquires new funds from industry sources or venture firms, it must recognize that it has ongoing obligations to the people of California.”

“She continued, 'CIRM has not responded in a meaningful way to many previous public interest suggestions or to independent reviews, including the one in 2008 by the state’s Little Hoover Commission. We hope the agency will not continue that pattern.' 

“'Today’s report from the IOM reaffirms the significance of the conflicts of interest and structural flaws that were built into the stem cell program from the beginning, and that continue to threaten its credibility and effectiveness. These are serious problems that the Center for Genetics and Society and other public interest voices pointed out even before the agency was approved by the 2004 ballot measure on which backers spent some $35 million. 

“'Many aspects of these early concerns remain directly relevant,' Darnovsky said. 'There is still no way for elected officials to provide oversight because the measure that created CIRM requires a 70% vote by both houses – more than a supermajority. The agency’s governing board is still tainted by its built-in conflicts of interest, and still includes no representation of the public beyond disease advocates. Members of the agency’s powerful Working Groups, including the one that reviews grant applications, are still not required to publicly disclose their individual financial interests.'”

More IOM-CIRM Coverage: One Story Notes Major 2007 Conflict Flaps at Stem Cell Agency

Additional coverage emerged this morning, including stories in the Los Angeles Times, the Nature web site and Businessweek. on a blue-ribbon report that recommended sweeping changes at the the $3 billion California stem cell agency

In the Times, California's largest circulation newspaper, Eryn Brown's story was headlined,

"Stem cell agency board criticized for conflicts of interest."

The article began,

"The board of California's stem cell funding agency is rife with conflicts of interest and should be restructured to improve the integrity of its grant-making process, according to a new report from independent experts convened by the national Institute of Medicine."“

In the San Diego U-T, reporter Bradley Fikes' article was the only piece in all the coverage to mention two major conflict-of-interest flaps at the agency in 2007.

One involved then CIRM board member John Reed, head of Sanford-Burnham in La Jolla, who tried to influence CIRM staff in connection with a grant to his organization, triggering an investigation by the state's political ethics commission. (Reed's actions were first disclosed by the California Stem Cell Report.) The other case involved inappropriate actions by four members of the 29-member board in an $85 million round. Ten applications were dumped from the round because of the directors' actions. The conflict issues were so rampant that only eight of the directors present at a December 2007 meeting could discuss the issues.

(See here, here and here.)

On the Nature news blog, Monya Baker had a thorough piece that said the agency “received a mixture of praise and hard-to-enact recommendations from an august scientific body.” She also wrote,

“It’s unclear what effect the report will have. Many of these recommendations run counter to requirements enshrined in the legislation that created CIRM, and the board of CIRM has heard similar recommendations before and failed to act on them.”

On the web site of the journal Science, Greg Miller wrote that IOM report "praises the California Institute for Regenerative Medicine (CIRM) as a 'bold social innovation' that provided a creative new source of funding that has turned the state into an international hub of stem cell research. But the IOM panel authoring the report also concluded that the funding agency’s organization and governance is not optimal."

Businessweek carried the AP story by Alicia Chang mentioned yesterday. The AP story also appeared on the San Francisco Chronicle and Sacramento Bee web sites and was also carried internationally on other web sites.  The Chronicle also had a staff story by Erin Allday.  
(An earlier version of this item did not contain the last sentence regarding the Allday story.)

Coverage of the IOM Report: Light but a Column with a Cutting Edge

News coverage has been light so far today of the Institute of Medicine's recommendations for an overhaul at the $3 billion California stem cell agency. But a Pulitzer Prize-winning columnist from the Los Angeles Times took a sharp knife to the agency's press release on the IOM report.

Michael Hiltzik, who is a regular critic of the agency, asked,

 "So how did CIRM react to the report? Even before the review panel's conference call with the press was completed, the agency issued a news release stating that the panel had 'praised' the agency 'for its ground breaking work in helping advance the science of stem cell research.'"If you wanted to know about the committee's criticisms, the first mention of those was in paragraph 9 of the news release. It quoted board Chairman Jonathan Thomas as promising to 'work on establishing a process to enable us to consider how best to proceed with reviewing the recommendations.' 

"By my count, that's seven steps it will take before actually acting on the recommendations. 

"As it happens, the panel's recommendations, which include creating a majority of independent board members without any potential conflicts of interest, track very closely to recommendations made by several previous outside reviews of CIRM, especially a 2009 study by the state's Little Hoover Commission.

"CIRM rejected almost every one, and it looks to be preparing to circle the wagons again against sensible improvements in the way it does business."

The Associated Press story by Alicia Chang popped up in two different forms on the Washington Post web site and in Ottowa and Spokane, among other places. Chang was on board for the IOM news conference and had this to say about CIRM from one of the IOM study group members.

“'They’re not broken but they’re bent,' said Sharon Terry, president of the nonprofit Genetic Alliance who was part of the panel. 'They need some correction.'”

Chang's story originally began,

“California has transformed into a powerhouse player in stem cell research, but the taxpayer-funded institute responsible for that needs an overhaul, a report released Thursday found.”

Another version, that appeared in Ottowa and Spokane and beyond, started this way,

“A report says California’s stem cell agency needs more independent oversight and recommends a restructuring to avoid the appearance of conflict of interest.”

Ron Leuty of the San Francisco Business, who is one of perhaps two reporters who regularly cover the stem cell agency, wrote,

“A review of California's stem cell research funding agency proposed changes to the agency's governing structure and commercial goals while praising its results so far. The 124-page report from the Institute of Medicine recycles many conflict of interest and intellectual property concerns that have dogged the San Francisco-based” agency.

Stephanie O'Neill at KPCC radio in Los Angeles also had a story.

The IOM and the CIRM Point of View

The California stem cell agency today looked at the study that it paid $700,000 for and decided the glass was half full.

The agency's press release on the 124-page report by the prestigious Institute of Medicine was headlined, “Institute of Medicine Report Praises Stem Cell Agency as a 'Bold Social Innovation.'”

The report also recommended sweeping changes at the agency, including stripping its governing board of the power to approve individual grants, overhauling the board to install a majority of independent directors and fundamentally altering the role of the 10 patient advocates on the 29-member board.