New Reviewers Appointed by California Stem Cell Agency

The governing board of the California stem cell agency this morning approved the consent calendar on the meeting's agenda. Those are matters that have no controversy. Today they included appointments of new scientific grant reviewers.

New Grant Reviewers for California Stem Cell Agency

Five new scientific grant reviewers are expected to be approved tomorrow by directors of the California stem cell agency, and at least four have backgrounds that might make them judges in the upcoming $40 million stem cell genomics round.

They include one scientist who once held $7.4 million in grants from the California stem cell agency. He is Martin Pera of the University of Melbourne in Australia. Pera was the first head of the USC stem cell program, serving from 2006 to 2011. The program was launched in the wake of the passage of Prop. 71, which created California's $3 billion stem cell program.

According to the University of Melbourne, Pera has done a significant amount of research in the area of cytogentics and genome mapping.

Scientific grant reviewers for CIRM all come from out-of-state. Pera is likely the first former CIRM grant recipient to be selected as one of the reviewers who make 98 percent of the decisions on the agency's grant applications. None are required to disclose publicly their financial or professional interests.

Other proposed scientific reviewers include:
Bradley Bernstein of Massachusetts General Hospital and Harvard, who is co-director of the epigenomics program at the Broad Institute.

Richard Gibbs, director of the human genome sequencing center at the Baylor College of Medicine.

Barry Rosen of the Wellcome Trust in the United Kingdom, who has done work in genetics and genome engineering.

Steven Jon Russell of the Harvard Medical School, who works in diabetes and completed the first outpatient trial of a treatment device described as a closed-loop artificial pancreas blood glucose control system.

Others being reappointed are Shelly Heimfeld of Hutchinson Cancer Research Center, Ihor Lemischka of Mount Sinai and Thomas Zwaka, also of Baylor.

The CIRM staff document prepared for tomorrow's meeting contains additional information on all the scientists.

CIRM Director Prieto on Disclosure of Reviewer Financial Interests

A member of the governing board of the $3 billion California stem cell agency is weighing in on an item on the California Stem Cell Report that called for public disclosure of the financial interests of the scientific reviewers, who make 98 percent of the decisions on awards by the agency.

Francisco Prieto, a Sacramento physician and a patient advocate member of the board, said in an email:

“ It seems to me there's a bit of 'damned if we do and damned if we don't' here. If the ICOC (the agency governing board) decides to listen to some of the members of the public who come to our meetings and overrule a recommendation of the Grants Working Group(GWG), we're slammed for letting emotion trump science, or bowing to special interests. If we just accept the rankings of the GWG and approve all their recommendations, we're criticized for not being truly independent.  I think we don't do it often (for good reason) but should and do retain the right to look at other factors besides those our scientific reviewers do, and make our own decisions about funding. We are ultimately responsible, not the scientific reviewers. 

“As for the issue of their disclosure of personal conflicts of interest, from what I've read of the NIH processes, ours are no less strict. The NIH requires that reviewers disclose any conflicts to their institutions which I believe must disclose them to the NIH, but I have not seen anything requiring them to disclose all their personal financial & other interests publicly, as we (ICOC members) have to.  When we were assembling our group of reviewers initially, the fear was that many of the best scientists would turn us down if we required them to make the kind of personal disclosures we have to. I don't know how many we might actually lose if that were the case, but as you know we do require them to disclose to CIRM, and they have to leave the room when any application for which they have a conflict is discussed.”

Our take: Prieto is right about the board being perched on the horns of a dilemma, which has a lot to do with Proposition 71, which created the agency, and American scientific traditions, which place an extraordinary value on the “integrity” of the review process. In this case, integrity refers to adherence to reviewers' scientific judgments.

Proposition 71 placed the legal authority for grant approvals in the hands of the CIRM board, which has overridden decisions by reviewers in only 2 percent of the cases since 2005. However, that was enough, with at least one high profile case coupled with public appeals, to cause the Institute of Medicine to raise concerns about the integrity of the CIRM grant review process. Traditionally, peer reviewers are deemed to be the most capable of making the scientific decisions about grant applications, rather than a board appointed by University of California chancellors and elected state officials.

Yet, if the board concedes the decisions to the grant reviewers, state law is likely to require public disclosure of their financial interests, a move that the board has opposed for years. Former CIRM Chairman Robert Klein repeatedly advised the board during its public grant approval processes that reviewers' actions were only ”recommendations” and that the board was actually making the decisions. However, it has long been apparent that the reviewers were making the de facto decisions. A CIRM memo in January confirmed that, producing the 98 percent figure.

The issues involving disclosure by reviewers, integrity of peer reviews, the language of Proposition 71 and state law are difficult and may, in some cases, be at odds.

However, it makes little difference what the NIH is doing. It is a much different organization and has had a history of conflict of interest problems that it has been trying to work through.

The trend in the academic and scientific research community has been towards more public disclosure rather than less because of many well-documented instances of problems. What is at stake is the public's faith in scientific research and the integrity of public institutions.

Our thanks to Prieto for his comments on this important subject.  

Time For Public Disclosure of Financial Interests of Stem Cell Agency Reviewers

Should the scientists who evaluate and score the applications for $3 billion in taxpayer funds be required to publicly disclose their financial interests?

No, says the California stem cell agency, despite concerns by the state auditor and the state's Fair Political Practices Commission (FPPC) that date back at least six years. The agency says that its governing board makes the decisions on the applications – not the grant reviewers – and that the members of the board fully disclose their economic interests.

However, last month the agency produced a document that sheds new light on the issue. The document confirms that the board rubber-stamps virtually all the reviewers' decisions, going along with their actions 98 percent of the time. The board exercised independent judgment on 28 out of 1,355 applications.

Why is this important? Here is what the state auditor said in 2007,

“(T)he FPPC believes that, under state regulations, working group members (including grant reviewers) may act as decision makers if they make substantive recommendations that are, over an extended period, regularly approved without significant amendment or modification by the committee. Thus, as decision makers, working group members would need to be subject to the conflict-of-interest code. This would mean that working groups would be subject not only to the (public) financial disclosure requirements of the Political Reform Act but also to the prohibition against a member participating in a government decision in which that member has a disqualifying financial interest and may be subject to the penalties that may be imposed on individuals who violate that act.”

The auditor recommended that the stem cell agency seek an attorney general's opinion on the matter, a recommendation the agency agency summarily dismissed seven months later..

Then interim CIRM President Richard Murphy, a former member of the agency's board and former president of the Salk Institute, replied to the auditor:

"We have given careful consideration to your recommendation and have decided it is not appropriate to implement at this time. In almost three years of operation and approval of four rounds of grants, the recommendations of the CIRM working groups have never been routinely and/or regularly adopted by the ICOC. Until the time that such a pattern is detected, the question you suggest we raise with the attorney general is entirely hypothetical, and is therefore not appropriate for submission. We will, however, continue to monitor approvals for such a pattern and will reconsider our decision if one emerges."

In the four rounds mentioned in Murphy's response, 100 percent of reviewer decisions were rubber-stamped by the board. In the other two rounds, the percentage was 95 and 96 percent.

Currently, scientific grant reviewers at the stem cell agency, all of whom are from out-of-state, disclose financial and professional conflicts of interest in private to selected CIRM officials. (See policy here.) From time to time, grant reviewers are excused from evaluating specific applications.

The CIRM governing board has resisted requiring public disclosure of the interests of reviewers. The subject has come up several times, but board members have been concerned about losing reviewers who would not be pleased about disclosing their financial interests.  Nonetheless, disclosure of interests among researchers is becoming routine in scientific research articles. Many universities, including Stanford, also require public disclosure of financial interests of their researchers. Stanford says,

“No matter what the circumstances -- if an independent observer might reasonably question whether the individual's professional actions or decisions are determined by considerations of personal financial gain, the relationship should be disclosed to the public during presentations, in publications, teaching or other public venues.”

The latest version of CIRM's conflict of interest rules are under review by the FPPC. They do not include any changes in public disclosure for grant reviewers. In view of the new information that confirms that reviewers are making 98 percent of the decisions on who gets the taxpayers' dollars, it would seem that it is long past due for public disclosure of both financial and professional interests of reviewers. Indeed, given the nature of scientific research and the tiny size of the stem cell community, disclosure of professional interests may be more important than financial disclosures.

As Francis S. Collins, head of the NIH, said concerning his organization's own strengthening of disclosure requirements,

"The public trust in what we do is just essential, and we cannot afford to take any chances with the integrity of the research process."

Here is the CIRM document concerning reviewers' decisions and governing board action. The table has not been posted on the CIRM website, but it was prepared for last month's meeting dealing with the Institute of Medicine's recommendations for sweeping changes at the agency, especially related to conflicts of interest.

CIRM Board's Record on Reviewer Grant Decisions by

New Info on Pay Raises for Grant Reviewers

Don Gibbons, chief communications officer for CIRM, has provided fresh information on the proposed compensation increases for scientific grant reviewers. In a comment on the “Whopping Pay Hike” item, he indicated this evening that the amount is not likely to exceed $4,500 per grant round per scientist. We appreciate that he has brought this new information to our readers' attention. We have also filed a response to his comment. Both can be found via the “recent comments” column to the left or by clicking on “comments” on the original item.

Whopping Pay Hike Proposed for CIRM Grant Reviewers

The California stem cell agency, which constantly stews about recruiting and keeping enough top notch scientists to review its grant applications, is now proposing to pay them $750 a day, which could total as much as $10,000 per reviewer for each grant round.

If the compensation reaches that level, it would be a 500 percent increase in the flat $2,000 that was previously provided.

The pay hike comes before the CIRM board later this week. In a memo, the CIRM staff said it was needed in order for the agency to be “competitive” in securing reviewers, who are usually well-known and respected scientists.

CIRM offered no figures for the overall estimated cost of the increase in what it calls "honorarium." But at $750-a-day, which amounts to $195,000 if it were applied on annual basis, the amount is pay – not honorarium.

We based our cost estimates on information provided in 2007 by Richard Murphy, then interim president of CIRM. Murphy also had served as head of the Salk Institute and as a member of CIRM board.

Murphy told the California Stem Cell Report that when he did grant reviews it took him one to two weeks to review the grants and write them up, including meeting time and travel. Based on that, the proposed pay for reviewers – which covers days of service, not just actual meetings -- could run from $3,750 to $10,000 per grant ground for each reviewer. Of course, the amount depends on how fast a reviewer works and could be less or more.

The number of grant reviewers actually used varies, depending on the need for specialists. However, 13 sit as regular members of the grant review group and many, many more as alternates or ad hoc members.

Murphy spoke to us at a CIRM board meeting during which the compensation was boosted from $500 a day to the flat $2,000. The $500 only applied to meeting days. The compensation does not include travel expenses, which are also reimbursed by CIRM.

As CIRM indicated, retaining skilled reviewers appears to be getting tougher. Lifting of the federal ban on hESC grants would certainly would seem to create more demand from the NIH for scientific reviewers who might also be recruited by CIRM. And the stem field generally is much more active than it was in 2005, when CIRM got started, generating more demand for reviewers. All of those reviewers also have their own personal research projects to attend.

The need for increased CIRM incentives is also likely linked to the absence of a chief scientific officer (CSO) at CIRM. One of the “the most important and least appreciated aspects of the CSO's role has been to personally beg, harangue and plead” with other scientists to serve as reviewers, as one person told us.

The post is now vacant after the resignation of Marie Csete earlier this year. Csete had served as CIRM reviewer and was well-respected and well-known in her field, giving her the heft to bring in reviewers.

It is likely to be some months before her post is filled.

CIRM also cited as justification for the pay increase an increasing future workload as grant rounds become more complex.

CIRM Grant Reviewer Verfaillie Linked to Investigations in Minnesota

A internationally known stem cell researcher who serves as a grant reviewer for the $3 billion California stem cell agency is at the heart of an inquiry at the University of Minnesota concerning the integrity of some of its stem cell research.

The matter involves Catherine Verfaillie (pictured) and New Scientist magazine, which raised concerns about the research. Verfaille is currently listed on the CIRM Web site as one of the scientists who make de facto decisions on research grant applications for hundreds of millions of dollars from the California Institute of Regenerative Medicine.

We queried CIRM two days ago about Verfaillie but the agency has not responded.

The research inquiries at the University of Minnesota involve scientists who worked in Verfaillie's lab or who were affiliated with her. She is now working at Katholieke Universiteit Leuven in Belgium but is still associated with the University of Minnesota. New Scientist once described her as running “one of highest-profile teams in stem-cell biology.”

Here is how Chris Williams of The Associated Press began his story last week on the research investigation,

“The University of Minnesota has launched its third internal investigation in two years into allegations of research misconduct....”

Jeremy Olson of the St. Paul Pioner Press wrote,

“In a familiar pattern, reporters from New Scientist magazine found images in a published study that appeared questionable and alerted U officials.

“The university already has retracted one stem cell study and corrected two others because of concerns raised by New Scientist. Having to launch yet another inquiry is an embarrassment for a university that has been viewed as a global expert in stem cell research....”

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said that the Minnesota case has implications that go beyond one researcher or institution.

According to reporter Williams,

"'What's unusual here is that you're starting to get other people involved," (Caplan) said. 'It's become a problem of a group, not an individual.'"

Williams continued,

“The Minnesota situation is also unusual, Caplan said, in that its researchers have been getting special scrutiny from New Scientist. He suspects there would be more questions of sloppiness or fraud at other universities if more outsiders were watching.

“There is particular pressure on scientists working in the stem cell field, with its mix of politics, the prestige of breakthroughs and the potential profits from patents.

"'I really can't think of too many areas that are more set up for somebody to cut corners than stem cell work,' he said.”

Peter Aldous and Eugenie Samuel Reich have been investigating the work at the University of Minnesota over several years. Their most recent piece on Aug. 5 said,

“Other stem cell biologists are disturbed that so many problems have been found in papers from a single institution. 'It's pretty discouraging," says Arnold Kriegstein of the University of California, San Francisco. Given the pressure on scientists in such competitive fields, he wonders what might emerge at other research centres if their publications were subjected to similarly close scrutiny.

"'It raises serious issues about how widespread this could be,' he says."

Aldous and Reich's Aug. 5 article has a full rundown on the cases they have investigated.

Conflicts of Interest, CIRM and Transparency

Do conflicts of interest exist among the scientists who make the de facto decisions on hundreds of millions of dollars in California grants for research related to embryonic stem cells?

The answer? Yes.

Even the California stem cell agency acknowledges that fact. Because of conflicts, the agency regularly excuses some of the scientists who review the grant applications from participating in specific cases.

But CIRM stoutly maintains that the financial and professional interests of reviewers are not suitable for release to the public or applicants. The agency contends the reviewers are only making recommendations. However, the reviewers' decisions are almost never rejected by CIRM's board of directors. The agency also has turned down a recommendation by the state auditor that it seek an opinion from the state attorney general on whether it should publicly disclose the reviewers' interests.

Trust us, the agency says. We will police the conflicts and assure that no abuses occur.

Rarely do rejected applicants raise conflict issues publicly. No one wants to offend the world's largest source of funding for human embryonic stem cell research. In August, however, one scientist brought up the question of conflicts at a meeting of the CIRM board of directors.

Steven Kessler, a scientific director at Advanced Cell Technology of Los Angeles, was not happy with the response he received from CIRM staff on a letter he wrote concerning what he said was a conflict of interest on the part of a unnamed reviewer.

According to the transcript of the meeting, here's how Kessler summarized his position for CIRM directors:

"If a grant reviewer has a financial relationship with company "X"...that is, he's receiving funding from that organization or he's expecting royalty income from some company by virtue of having licensed technology to that company and that reviewer is sitting in on reviews from other for-profit organizations...and doesn't recommend those for funding, to us, from a business perspective, that's a conflict of interest."

Kessler said he had cited "numerous instances" of conflicts on the part of the reviewer, where there would be "every incentive to help impede the competition for the company that he has a relationship with.".

Kessler said,

"I was told that the way CIRM interprets its own conflict of interest policy, the example I gave you was not a conflict of interest."

At that point CIRM Chairman Robert Klein cut off Kessler, declaring that the directors needed to discuss the names for CIRM-funded labs before going to lunch.

Kessler's comments followed a discussion in which Klein and other directors expressed concern about reviewers quitting if they were subject to public complaints.

Klein said,

"To the extent that (applicants) are criticizing peer reviewers, which is sometimes common, we're going to lose our peer reviewers."

On Sept. 14, we asked CIRM for a copy of Kessler's conflict-of-interest letter. On Oct. 22, more than five weeks later and after repeated follow-up queries, the agency declined to release the letter.

Initially, Don Gibbons, chief communications officer for CIRM, said there was a question of redaction of material from the letter. Then he said our inquiry was lost by CIRM's interim general counsel. Ultimately, on Oct. 22, Gibbons said,

"Our interim general counsel has determined that the Kessler letter is part of the grant application process and as such is not a public document."

We asked for the legal reasoning behind that statement. On Oct. 29, Gibbons quoted interim counsel Ian Sweedler as saying,

"Applicants need to know that they can contact CIRM with information about potential conflicts, and that they can do that without leveling public allegations against a professional colleague."

Obviously conflicts of interest can at times involve judgment calls. CIRM also places a burden on its reviewers, all of whom come from out-of-state and cannot apply for CIRM grants. Marie Csete, now CIRM's chief scientific officer, commented last year on the situation when she was a reviewer prior to her employment at CIRM. Among other things, she said that she and the other reviewers were being asked to fund the work of their competitors.

CIRM's overriding concern has been the care and feeding of reviewers. We acknowledge that they need considerable attention. However, the main issue here is the stewardship of public funds and the integrity of a state government process involving billions of dollars. From its birth, CIRM has wrestled with problems spawned by the ballot initiative that created the research program. CIRM was deliberately cobbled together with built-in conflicts starting at the very top. The chief beneficiaries of CIRM's largess sit on its board of directors and set the rules for grants and control the process.

The bounty from CIRM is huge. Here is a list of CIRM recipient institutions (with grant totals) which have or had employees or representatives on the CIRM board of directors: Stanford, $94 million; UC San Francisco, $82 million; UCLA, $51 million; UC Irvine, $51 million; USC, $48 million; Sanford (San Diego) Consortium, $43 million; UC Davis, $36 million; UC San Diego, $33 million; UC Berkeley, $29 million; UC Santa Cruz, $17 million; Burnham, $18 million; Salk Institute, $16 million; Scripps, $9 million; UC Merced, $8 million; UC Santa Barbara, $7 million; UC Riverside, $6 million; Caltech, $2 million, and City of Hope, $2 million.

The built-in conflicts at CIRM are not likely to change, short of another ballot measure. They are enshrined in the state Constitution, a move by Prop. 71 writers who wanted to make CIRM immune to normal government oversight.

However, handing out billions behind closed doors with no outside scrutiny is a recipe for abuse. State ethics officials are already looking into the attempt by one CIRM director to influence CIRM staff on behalf of his institution. Should a major scandal erupt, it would ill serve the agency, the people of California and the cause of science.

If only to protect itself, the agency should comply with its repeated promise to adhere to the highest standards of openness and transparency and publicly release the statements of the economic and professional interests of its reviewers.

(Further note: Kessler also declined to release his letter to us. The CIRM grant review committee meets next Wednesday and Thursday in San Francisco to review applications for $66 million in public funds. The review sessions are closed but the public may comment on Wednesday morning.)

CIRM Providing Some Early Background Info on Directors Meeting

The California stem cell agency today posted the agenda for its Aug. 12-13 meeting at Stanford, along with some background material.

The background material is a good start on helping the public understand what is to be discussed and acted on by the directors of the $3 billion public enterprise. We are looking forward to more in the next few days.

The background information on one item has clarified what is actually to be discussed when directors take up "consideration of annual report on CIRM contracts and interagency agreements." On Sunday, we speculated that the item could be a proposal to change from quarterly to annual the reporting requirements to directors on outside contracts. In fact, the item appears to be simply the 2007-08 annual report on outside contracting expenditures.

Other background material now available includes:

Draft language for a "grandfathering" provision on stem cell lines. Directors will be asked to authorize a procedure for petitioning them to designate stem cell lines derived before November 2006 as acceptably derived for use in CIRM-funded research.

The names and brief bios of proposed alternate members for the Grant Review Group: Sangeeta N. Bhatia of MIT, Paula Marie Bokesch of Hospira, Inc., Mark Furth of the Wake Forest Baptist Medical Center, Marcie Glicksman of Brigham and Women's Hospital, Kurt Gunter of Hospira, Inc., Paul Kulesa of the Stowers Institute for Medical Research, Hai-Quan Mao of John Hopkins, Todd McDevitt of Georgia Institute of Technoloogy/Emory University, Alan Russell of the University of Pittsburgh and Shuichi Takayama of the University of Michigan.

Clarification

On Dec. 5 in the item below, we reported that CIRM was considering raising the honorarium for scientists who review grant applications from $500 to $2,000 daily. The increase would actually be to $2,000 for any meeting, whether it is one or two days, and include preparation. Generally the grant review sessions have not lasted more than one or two days. Reviewer's expenses are covered as well.

Interim CIRM President Richard Murphy also pointed out to us that when he did grant reviews in the past that it took him one to two weeks to review the grants and write them up, including meeting time and travel.

(Editor's note: Originally this item was labelled as a correction. However, in reviewing the material from CIRM, the agency's material was ambiguous about whether the $2,000 was a flat fee.)