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

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

Stem Cell Directors Discussing CIRM's Science Program

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

Review of CIRM Science Program Continuing

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

California Stem Cell Agency Directors Begin IOM Meeting

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

Inside the Grant Review Process at the California Stem Cell Agency

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

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

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

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

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

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

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

IOM Description of CIRM Grant Review Process

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Texas and California: Conflicts, Research Funding and Controversy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fikes also reported,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Stem Cell Agency Chair Pressing for Consensus on IOM Recommendations

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

Writing on the agency's blog, Thomas said,

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

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

He continued,

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

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

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

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

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

In his blog item, Thomas sounded this final note.

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

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

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

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

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

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

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

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

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

Knoepfler said,

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

Knoepfler also wrote,

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Live Audiocast Available for Next Week's CIRM-IOM Meetings

The California stem cell agency will provide a live audiocast of next week's critical discussions of action on the sweeping recommendations proposed for the agency by the Institute of Medicine.

Instructions for hooking into the telephonic arrangement can be found on the agendas for Wednesday and Thursday. Also expected to be posted soon on the Wednesday agenda are recommendations by CIRM Chairman J.T. Thomas.

The audiocast will only provide the opportunity to listen and no opportunity to provide testimony. If you are interesting in making suggestions or comments ahead of the meeting, email them to info@cirm.ca.gov. The public can also testify at the board meeting.

The meeting is scheduled for the Claremont Hotel in the Berkeley hills across the bay from CIRM's San Francisco headquarters.

California Stem Cell Face-Off: CIRM Directors Wrestle with Tough IOM Recommendations

Two days next week at the posh Claremont Hotel in the Berkeley hills could settle the fate of California's $3 billion stem cell agency.

At 9 a.m. next Wednesday, the governing board of the state research effort will begin a critical, two-day public session. On the table will be the $700,000, blue-ribbon report from the prestigious Institute of Medicine (IOM). The study recommends sweeping changes in the structure and operations of the California Institute of Regenerative Medicine (CIRM), as the stem cell agency is formally known.

The IOM report alone poses major challenges for the agency. But the recommendations are freighted with even more significance. Below the surface lies the hard fact of CIRM's dwindling resources and possible demise. In less than four years – without either renewed public support or private contributions – the research effort will begin a shriveling, downward spiral.

Claremont Hotel

The IOM report places a special burden on the agency governing board. The board paid the IOM to evaluate its performance. In 2010, then CIRM Chairman Robert Klein trumpeted the value of an IOM study, saying it would serve as a springboard for a new, multibillion-dollar state bond measure for the agency(see here and here). Given the state's difficult financial condition – not to mention the position of potential private sector investors – winning approval of that kind of investment will be more than difficult. 

California's major newspapers already have editorially backed the IOM proposals. Indeed, if the directors choose to ignore the major IOM recommendations, they will hand opponents a devastating weapon, one that could be used to convince voters to reject any proposal for continued funding. The board would also give private investors more major reasons to say no to CIRM pitches for cash.

Under Klein's leadership, the 29-member board has rejected similar proposals for changes in the past. When the IOM presented the study to the board just last month, the reception was not much different. Several board members bristled. One influential board member, Sherry Lansing, chair of the University of California board of regents, said the directors' “hands are tied” because some of the recommendations might require a vote of the people. Her comments echoed similar statements from Klein in 2009, when he said board members would violate their oath of office if they supported recommendations for changes that he opposed.

The IOM discussion in December, however, was relatively brief and less than definitive. Klein has been off the board since June 2011, replaced by Los Angeles bond financier Jonathan Thomas, who is regarded as a welcome change by a number of board members.

Nonetheless, the recommendations of the IOM could mean that some members of the board would lose their seats; others would lose important roles in the grant-award process or within the agency itself. Conflict of interest rules would be tightened. In some ways, the board would lose power, which would be shifted to the president. The board would no longer vote on individual applications – only a slate recommended by reviewers. Applicants for CIRM awards would be directly affected, being barred from making the sort of direct and public appeals that clogged the CIRM board meetings last year. And that would be just the beginning.

Thomas, the CIRM chairman, is expected to make his recommendations for action on the report, although they have not yet been posted on the CIRM web site. Under what might be considered “normal” leadership, Thomas would be testing sentiment among board members via personal conversations and phone calls. However, in California that would be illegal – a violation of open meeting laws that bar what are called “serial meetings” at nearly all public agencies.

Thomas' task is not easy. Rounding up a majority vote for anything significant among 29 strong-minded individuals is not simple. But it is even more difficult when facing a board that has a tradition of consensus management and oversight.

The site of next week's meetings is interesting. The nearly 100-year-old, iconic Claremont hotel has a troubled financial history. It was up for sale for $80 million last spring but there were no takers. In the early 20th century, the property on which it is located was lost and won in a checkers game in Oakland, or so the story goes.

The stakes are also high for the California stem cell agency. Moves next week by directors could easily determine whether CIRM becomes nothing more than an interesting scientific footnote or establishes a path that will lead it to long-lasting leadership in regenerative medicine.

Nature Biotechnology: California Stem Cell Agency Receives 'Stinging Rebuke'

The headline this week in Nature Biotechnology read: “IOM smacks down California Institute of Regenerative Medicine.”

The story by Senior Editor Laura DeFrancesco said that the $3 billion California stem cell agency “received a stinging rebuke of much of the way it has been carrying out its business by a group of independent reviewers.”

At the same time, DeFranesco wrote that the blue-ribbon, Institute of Medicine panel “praised the courage and vision of the individuals who spearheaded the program as well as those toiling in the CIRM office in San Francisco.”

The Nature Biotechnology piece covered familiar ground for many readers, summarizing the IOM's sweepingrecommendations last month, including those dealing with the built-in conflicts of interest on the agency's 29-member governing board.

DeFrancesco wrote that is unclear whether the agency will move to adopt any of the recommendations from the panel, many of which have been rejected in the past.

Some members of the CIRM governing board last month bristled at some of the recommendations. The board is scheduled to discuss the IOM report, for which it paid $700,000, at a public meeting Jan. 23 in Berkeley. Patient advocates are already organizing a turn-out to lobby against some recommendations.  

Roman Reed is Stem Cell Person of 2012; Leigh Turner Runner-up

Roman Reed, a Fremont, Ca., patient advocate, this week was named Stem Cell Person of 2012 by the Knoepfler Stem Cell Lab at UC Davis, which cited Reed for energizing a new generation of advocacy.

Roman Reed (left) and Paul Knoepfler
Knoepfler Lab photo

UC Davis stem cell scientist Paul Knoepfler awarded Reed $1,000 from his personal funds. The ceremonial check appears to be close to four-feet long in a photo taken in Knoepfler's lab.

Knoepfler wrote on his blog that Reed made a “tremendous difference” in 2012. The researcher said,

“One of the most notable was catalyzing the TJ Atchison Spinal Cord Injury Research Act in Alabama, which provides $400,000/year in funding for research. Of course, TJ and many others who helped make this possible also deserve great credit and have my admiration, but Roman provided key leadership. Here in California, Roman’s Law supported its 11th year of grants all eligible for all forms of stem cell research. Roman informs me that it funded $749,00 overall and approximately $200,000 in stem cell funding. 

“In addition, Roman in 2012 mentored and energized a whole new generation of advocacy from young, energetic leaders: TJ Atchison, Katie Sharify, Richard Lajara and Tory Minus.”

Knoepfler personally made the decision on the award, but also conducted an advisory poll that Reed won. Knoepfler wrote,

Leigh Turner
U of Minn photo

“Only 6% behind Roman was the amazing activist Ted Harada followed by Roman’s dad the remarkable Don Reed, the wonderful Judy Roberson, and the super Katie Sharify nearly all tied for third. Next after them was the relative new kid in stem cell town, Leigh Turner.”

Knoepfler named Turner, an associate professor at the Center for Bioethics at the University of Minnesota, as the official runner-up in the contest, No. 2 behind Reed. Knoepfler wrote,

“Leigh took the courageous, outside-the-box step in 2012 of contacting the FDA to investigate Celltex when he perceived patients could be at risk. As “thanks” for his action, he was put under enormous pressure and there was talk of possible litigation against him. Pressure was applied to his employer, the University of Minnesota. We’ll never know for sure, but from everything that I know I believe that Leigh’s actions directly led to prompt FDA action, which otherwise might not have happened at all or until much later. In my opinion, Leigh’s act of courage, helped make hundreds of patients safer in a direct way and indirectly may have set a higher standard for the field of stem cell treatments.”

BioTime Stock Jumps 22 Percent in Two Days in Wake of Geron Deal

The stock price of Biotime, Inc., of Alameda, Ca., shot up more than 12 percent today following the announcement of a complex deal that will give it the stem cell assets of Geron Corp., the first firm to launch a clinical trial for an hESC therapy.

Geron stock price Jan. 2-8
Google chart

BioTime stock closed at $3.88, up 43 cents or 12.46 percent. That followed a 9.6 percent gain yesterday. Geron's stock closed at $1.63, up three cents or 1.9 percent.

News coverage of the deal was light with our tracking showing only one story so far today on The Scientist magazine web site.

BioTime Buys Geron's Stem Cell Assets, Including hESC Clinical Trial

Geron Corp., which pioneered the first clinical trial of an hESC therapy, today sold its stem cell business to another San Francisco Bay Area firm whose two top executives were once CEOs at Geron.

Michael West
BioTime photo

The total value of the complex deal was not clear from the public statements released by Geron and the acquiring firm, BioTime, Inc., of Alameda, but an unidentified outside investor is adding $10 million to transaction.

In a telephone interview this evening, Michael West, CEO of BioTime, said that as a result of the deal his firm will hold 600 patents and patent applications involving stem cells. He said the aggregation should help in attracting financial interest in the firm and its efforts.

West founded Geron in 1990. BioTime Acquistion Corp., the BioTime subsidiary that is picking up the Geron assets, is headed by Tom Okarma, who was Geron's CEO from 1999 to 2011.

After Okarma left the firm in 2011, Geron abruptly jettisoned its stem cell business along with the clinical trial. Geron has been looking since then for a buyer for the assets.

Tom Okarma
Geron photo

Only a few months prior to the Geron decision in 2011, the California stem cell agency had signed a $25 million loan agreement with Geron to support the clinical trial. The company paid back with interest the amount of the loan that it had received.

Information from the two companies did not specify whether BioTime will begin seeking additional participants in the clinical trial. Nor did BioTime indicate whether it would seek additional funding from the state stem cell agency.

However, West said during the telephone interview that he has an “open mind” about working with CIRM. Last year, agency officials indicated an interest in continuing to support the clinical trial. West said BioTime had already hired some employees that were laid off by Geron, including its patent attorney. He said that he hoped to reassemble at least part of Geron's now scattered stem cell team.

According to the Geron press release, when the deal is officially concluded in September, “it is anticipated that Geron stockholders would own approximately 21% of BAC, BioTime would own approximately 72%, and a private investor would own approximately 7% after an additional $5 million investment in BAC.”

For its new operations, BioTime has leased space in Menlo Park that Geron once used for its stem cell business.

Both firms are publicy traded. BioTime's stock price closed at $3.45 today and had a 52-week high of $6.35 and a low of $2.67. Geron closed at $1.60 and had a 52-week high of $2.99 and a low of 91 cents.

Here is a link to an article in the San Francisco Business Times about the deal. Here are links to the BioTime press release, a BioTime FAQ and the Geron press release.